95715-87-0

Basic information

• Product Name: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE
• Synonyms: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE;TERT-BUTYL-(R)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE;(R)-4-FORMYL-2,2-DIMETHYL-OXAZOLIDINE-3-CARBOXYLIC ACID TERT-BUTYL ESTER;(R)-(+)-3-BOC-2,2-DIMETHYL-OXAZOLIDIN-4-CARBALDEHYDE;(R)-3-BOC-4-FORMYL-2,2-DIMETHYL-1,3-OXAZOLIDINE;1,1-DIMETHYLETHYL-(R)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE;(+)-n-boc-n,o-isopropylidene-d-serinal;(r)-(+)-3-boc-2,2-dimethyloxazolidine-4-carboxaldehyde
• CAS NO: 95715-87-0
• Molecular Formula: C₁₁H₁₉NO₄
• Molecular Weight: 229.27
• Product Categories: pharmacetical;Amiens;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 95715-87-0.mol
• Article Data: 44

Chemical Properties

• Boiling Point: 67 °C/0.3 mmHg(lit.)
• Flash Point: 107 °C
• Appearance: Colorless to pale yellow/Oil
• Density: 1.06 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.000972mmHg at 25°C
• Refractive Index: 1.445-1.447
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform, Dichloromethane, Ethyl Acetate
• PKA: -3.26±0.60(Predicted)
• Sensitive: Air Sensitive
• BRN: 3651554
• CAS DataBase Reference: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE(95715-87-0)
• EPA Substance Registry System: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE(95715-87-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 37/39-26-36-60-37-23
• WGK Germany: 3
• Hazardous Substances Data: 95715-87-0(Hazardous Substances Data)

Usage

Uses

(R)-(+)-3-Boc-2,2-dimethyloxazolidine-4-carboxaldehyde is used in the preparation of fluorinated analogs of glutemic and glutamine.

InChI:InChI=1/C11H19NO4/c1-10(2,3)16-9(14)12-8(6-13)7-15-11(12,4)5/h6,8H,7H2,1-5H3/t8-/m0/s1

Synthetic route

tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (108149-63-9, 108149-65-1) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Stage #1: tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate With oxalyl dichloride In dichloromethane; dimethyl sulfoxide at -60 - -45℃; for 0.666667h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane; dimethyl sulfoxide at -45℃; Inert atmosphere;	100%
With Dess-Martin periodane In dichloromethane for 2h; Ambient temperature;	93%
With Dess-Martin periodane; 1-butyl-3-methylimidazolium Tetrafluoroborate at 20℃; for 4h; Dess-Martin oxidation;	90%

(R)-N,O-isopropylidenyl-2-(N-tert-butyloxycarbonylamino)-3-oxo-propanamide-N,O-dimethyl-hydroxyamine (167102-62-7) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 0.5h;	100%
With lithium aluminium tetrahydride In 2-methyltetrahydrofuran at 0℃;	100%
With lithium aluminium tetrahydride In tetrahydrofuran for 2.33333h; Inert atmosphere; Cooling;	92%
With sodium bis(2-methoxyethoxy)aluminium dihydride In toluene at 0 - 30℃; for 3h;	100 g

methyl [(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]carboxylate (108149-60-6, 95715-86-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With diisobutylaluminium hydride In toluene at -60 - 0℃; for 2.5h;	95%
With diisobutylaluminium hydride In toluene at -78 - -70℃; for 4h; Inert atmosphere;	89%
With diisobutylaluminium hydride In toluene at -78℃; for 2h;	85%

(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid (660852-86-8) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 0℃; for 2h; Swern Oxidation;	85%

2,2-dimethyl-oxazole-3-carboxylic acid tert-butyl ester + dicarbonylacetylacetonato rhodium (I) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + tert-butyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate (95715-87-0, 102308-32-7, 144070-30-4, 127589-93-9)

Conditions	Yield
With 2,2',2'',2'''-(1,2-phenylenebis((1R,3R)-tetrahydro-5,8-dioxo-1H-(1,2,4)diazaphospholo(1,2-a)pyridazine-2,1,3(3H)-triyl))tetrakis(N-(1S)-1-phenylethyl)-benzamide In tetrahydrofuran at 55℃; under 7240.26 Torr; for 72h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	A 71% B n/a

(S)-2,2-dimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester 4-methyl ester (95715-86-9, 108149-60-6) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With diisobutylaluminium hydride In toluene at -80℃; for 4h; Automated synthesizer;	71%

D-Serine (312-84-5) + di-tert-butyl dicarbonate (24424-99-5) + 2,2-dimethoxy-propane (77-76-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multistep reaction;	51%

methyl [(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]carboxylate (108149-60-6, 95715-86-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (108149-63-9, 108149-65-1)

Conditions	Yield
With diisobutylaluminium hydride In toluene at -78℃;	A 40% B 8%

1,1-dimethylethyl 4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate → (4S)-4-formyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (102308-32-7) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With oxalyl dichloride; dimethyl sulfoxide; triethylamine 1.) CH2Cl2, -78 deg C, 15 min, 2.) -78 deg C to r.t.; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

(R)-4-(1,2-Dihydroxy-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With sodium periodate; silica gel In dichloromethane Ambient temperature; Yield given;

D-Serine (312-84-5) + (CH3)2CX, (CH3)3CHOCOX → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Yield given. Multistep reaction;

(R)-N-tert-butoxycarbonyl serine (3262-72-4, 3850-40-6, 6368-20-3, 90582-28-8, 84311-18-2) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 86 percent / K2CO3 / dimethylformamide / 1.5 h / 0 - 20 °C 2: 80 percent / p-TsOH / benzene / 1 h / Heating 3: 75 percent / DIBAL-H / toluene / 2 h / -78 °C View Scheme
Multi-step reaction with 3 steps 1: N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, N-methylmorpholine / CH2Cl2 / 1 h / -15 °C 2: BF3*Et2O / acetone / 1.5 h / Ambient temperature 3: 100 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: 0.5 h / 0 °C 2: 80 percent / TsOH*H2O / benzene / 0.5 h 3: 85 percent / diisobutylaluminum hydride (DIBAL) / toluene / 2 h / -78 °C View Scheme

2-(tert-butoxycarbonylamino)-3-hydroxypropionic acid methyl ester (95715-85-8) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / p-TsOH / benzene / 1 h / Heating 2: 75 percent / DIBAL-H / toluene / 2 h / -78 °C View Scheme
Multi-step reaction with 3 steps 1: 75 percent / TsOH*H2O / benzene / Heating 2: 96 percent / NaBH4, LiCl / ethanol; tetrahydrofuran / 4 h / Ambient temperature 3: 1.) trifluoroacetic anhydride, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) CH2Cl2, from -78 deg C to 25 deg C View Scheme
Multi-step reaction with 2 steps 1: 80 percent / TsOH*H2O / benzene / 0.5 h 2: 85 percent / diisobutylaluminum hydride (DIBAL) / toluene / 2 h / -78 °C View Scheme

di-tert-butyl dicarbonate (24424-99-5) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaOH / dioxane; H2O / 48 h / 0 - 20 °C 2: N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, N-methylmorpholine / CH2Cl2 / 1 h / -15 °C 3: BF3*Et2O / acetone / 1.5 h / Ambient temperature 4: 100 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1: 100 percent / Et3N / tetrahydrofuran / a) RT, 6 h, b) 50 deg C, 2 h 2: 98 percent / LiBH4 / tetrahydrofuran / 12 h / Ambient temperature 3: 98 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 4: 95 percent / H2 / Pd/C / ethyl acetate / 24 h / Ambient temperature 5: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme
Multi-step reaction with 4 steps 1: 1 N NaOH / dioxane / 1.) 5 deg C, 30 min, 2.) RT, 3.5 h 2: 0.5 h / 0 °C 3: 80 percent / TsOH*H2O / benzene / 0.5 h 4: 85 percent / diisobutylaluminum hydride (DIBAL) / toluene / 2 h / -78 °C View Scheme

tert-butyl N-[(1R)-1-(hydroxymethyl)-2-[methoxy(methyl)amino]-2-oxo-ethyl]carbamate (167102-61-6) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: BF3*Et2O / acetone / 1.5 h / Ambient temperature 2: 100 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 2.33 h / Inert atmosphere; Cooling View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / acetone / 0.05 h / 25 - 30 °C 2: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / 0 - 30 °C View Scheme

N-(tert-butoxycarbonyl)-L-serine methyl ester (2766-43-0) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: imidazole / CH2Cl2 / 12 h / Ambient temperature 2: LiBH4 / tetrahydrofuran / 12 h / Ambient temperature 3: 94 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 4: 98 percent / Bu4NF / tetrahydrofuran / 2 h / Ambient temperature 5: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: 93 percent / BF3OEt2 / acetone / 12 h / Ambient temperature 2: 78 percent / DIBAL-H / toluene / 1.5 h / -78 °C View Scheme
Multi-step reaction with 5 steps 1.1: 1H-imidazole / dichloromethane / 0 - 20 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 1.5 h / 0 °C / Inert atmosphere 3.1: toluene-4-sulfonic acid / toluene / 1.5 h / Reflux; Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 - 20 °C 5.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.58 h / -78 °C 5.2: 0.08 h / -78 - 0 °C View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / dichloromethane / 3 h / 25 °C / Automated synthesizer 2: diisobutylaluminium hydride / toluene / 4 h / -80 °C / Automated synthesizer View Scheme

(S)-tert-butyl (1-hydroxy-4-(methylthio)butan-2-yl)carbamate (51372-93-1) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 95 percent / BF3*Et2O / acetone / Ambient temperature 2: 93 percent / NaIO4, NaHCO3 / methanol; H2O / 0 °C 3: 69 percent / various solvent(s) / 6 h / 175 - 180 °C 4: OsO4, NMO / acetone / Ambient temperature 5: NaIO4, SiO2 / CH2Cl2 / Ambient temperature View Scheme

N-(tert-butyloxycarbonyl)-O-benzyl-L-serinol (79069-15-1) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 98 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 2: 95 percent / H2 / Pd/C / ethyl acetate / 24 h / Ambient temperature 3: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

methyl O-benzyl-N-(tert-butoxycarbonyl)-L-serinate (80963-10-6) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 98 percent / LiBH4 / tetrahydrofuran / 12 h / Ambient temperature 2: 98 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 3: 95 percent / H2 / Pd/C / ethyl acetate / 24 h / Ambient temperature 4: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

tert-butyl (4S)-2,2-dimethyl-4-vinyl-1,3-oxazolidine-3-carboxylate (133625-87-3) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: OsO4, NMO / acetone / Ambient temperature 2: NaIO4, SiO2 / CH2Cl2 / Ambient temperature View Scheme

methyl (2S)-3-(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)-2-[(tert-butoxy)carbonylamino]propanoate (159846-14-7) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: LiBH4 / tetrahydrofuran / 12 h / Ambient temperature 2: 94 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 3: 98 percent / Bu4NF / tetrahydrofuran / 2 h / Ambient temperature 4: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

(S)-4-Benzyloxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (198417-68-4) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / H2 / Pd/C / ethyl acetate / 24 h / Ambient temperature 2: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

tert-butyl [(1R)-2-(tert-butyldiphenylsilyloxy)-1-(hydroxymethyl)-ethyl]carbamate (198417-69-5) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 2: 98 percent / Bu4NF / tetrahydrofuran / 2 h / Ambient temperature 3: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

(R)-4-(tert-Butyl-diphenyl-silanyloxymethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (198417-70-8) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / Bu4NF / tetrahydrofuran / 2 h / Ambient temperature 2: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

(S)-2,2-Dimethyl-4-(2-methylsulfanyl-ethyl)-oxazolidine-3-carboxylic acid tert-butyl ester (197218-81-8) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / NaIO4, NaHCO3 / methanol; H2O / 0 °C 2: 69 percent / various solvent(s) / 6 h / 175 - 180 °C 3: OsO4, NMO / acetone / Ambient temperature 4: NaIO4, SiO2 / CH2Cl2 / Ambient temperature View Scheme

(S)-4-(2-Methanesulfinyl-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (197218-82-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 69 percent / various solvent(s) / 6 h / 175 - 180 °C 2: OsO4, NMO / acetone / Ambient temperature 3: NaIO4, SiO2 / CH2Cl2 / Ambient temperature View Scheme

2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile (58632-95-4) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: Et3N / dioxane; H2O 2: methanol 3: CSA / acetone 4: LiAlH4 / diethyl ether / 0 °C 5: -78 °C / Swern ox. View Scheme

(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)propanoate (126645-26-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 1.5 h / 0 °C / Inert atmosphere 2.1: toluene-4-sulfonic acid / toluene / 1.5 h / Reflux; Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 - 20 °C 4.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.58 h / -78 °C 4.2: 0.08 h / -78 - 0 °C View Scheme

(R)-[1-(tert-butyl-dimethyl-silanyloxymethyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester (152491-85-5) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 1.5 h / Reflux; Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 - 20 °C 3.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.58 h / -78 °C 3.2: 0.08 h / -78 - 0 °C View Scheme

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (108149-63-9, 108149-65-1)

Conditions	Yield
With zirconium(IV) tetraisopropoxide 2-propanol; 1,1'-bi-2-naphthol In toluene at 20℃; for 4h;	100%
With sodium tetrahydroborate In methanol at 0℃; for 1h;	84%
With zirconium(IV) tetraisopropoxide 2-propanol; 4 Angstroem MS; 1,1'-bi-2-naphthol In isopropyl alcohol; toluene at 20℃; for 12h;	70%
With sodium tetrahydroborate In tetrahydrofuran; isopropyl alcohol for 0.5h;	64%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + allylmagnesium bromide (1730-25-2) → 1,1-dimethylethyl (4R)-(1'-hydroxy-3'-butenyl)-2,2-dimethyl-3-oxazolidinecarboxylate (220317-60-2)

Conditions	Yield
	100%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + (carbethoxyethylidene)triphenylphosphorane (21382-82-1) → ethyl 2-methyl-3-[3-(tert-butoxycarbonyl)-2,2-dimethyl-(4S)-oxazolidinyl]prop-(2E)-enoate (916912-39-5)

Conditions	Yield
In dichloromethane at 20℃; for 12h;	100%
In benzene Wittig reaction; Reflux;	84%
In dichloromethane at 20℃;

O-methylresorcine (150-19-6) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → tert-butyl (R)-4-((R)-hydroxy(2-hydroxy-4-methoxyphenyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate (925703-63-5)

Conditions	Yield
Stage #1: O-methylresorcine With methylmagnesium chloride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In dichloromethane at 0 - 20℃; for 15h;	100%

C27H31N5O6S*2ClH + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → C38H50N6O9S (1111235-29-0)

Conditions	Yield
Stage #1: C27H31N5O6S*2ClH; (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine With sodium tris(acetoxy)borohydride; triethylamine In dichloromethane at 20℃; for 16h; Stage #2: With water; potassium carbonate In dichloromethane at 20℃;	100%

1-ethynyl-4-(n-pentyl)benzene (79887-10-8) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → C24H35NO4 (1207432-32-3)

Conditions	Yield
Stage #1: 1-ethynyl-4-(n-pentyl)benzene With n-butyllithium In tetrahydrofuran; hexane at -20℃; for 2h; Inert atmosphere; Stage #2: With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #3: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In tetrahydrofuran; hexane at -78 - -60℃; for 5h; Inert atmosphere;	100%

Sesamol (533-31-3) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → tert-butyl (R)-4-((R)-hydroxy(6-hydroxybenzo[d][1,3]dioxol-5-yl)methyl)-2,2-dimethyloxazolidine-3-carboxylate (925703-84-0)

Conditions	Yield
Stage #1: Sesamol With methylmagnesium chloride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In dichloromethane at 0 - 20℃; for 15h;	99%

diazoacetic acid ethyl ester (623-73-4) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (2E',4S)-4-(2'-ethoxycarbonyl-vinyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (134525-18-1, 131713-27-4, 144070-31-5, 149406-02-0)

Conditions	Yield
With Fe(TCP)Cl; polyethylene supported arsine; polymethylhydrosiloxane In toluene at 110℃; for 12h; Wittig type reaction; Inert atmosphere; stereoselective reaction;	99%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + 4-methylbenzo[1,3]dioxol-5-ol (187040-03-5) → (R)-4-[(R)-Hydroxy-(6-hydroxy-7-methyl-benzo[1,3]dioxol-5-yl)-methyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (654643-98-8)

Conditions	Yield
With methylmagnesium chloride In tetrahydrofuran; dichloromethane at 20℃;	98%
Stage #1: 4-methylbenzo[1,3]dioxol-5-ol With methylmagnesium chloride In tetrahydrofuran Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In dichloromethane Further stages.;	98%
Stage #1: 4-methylbenzo[1,3]dioxol-5-ol With methylmagnesium chloride In tetrahydrofuran; hexane at 20℃; for 0.5h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In tetrahydrofuran; hexane; dichloromethane at 20℃;	98%

3-bromo-3,3-difluropropene (420-90-6) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → C14H23F2NO4 (1056467-63-0)

Conditions	Yield
With indium; lithium iodide In N,N-dimethyl-formamide	98%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + (cyclopropylmethyl)triphenylphosphonium bromide (14799-82-7) → (S)-tert-butyl 4-(2-cyclopropylvinyl)-2,2-dimethyloxazolidine-3-carboxylate (1222186-28-8)

Conditions	Yield
Stage #1: (cyclopropylmethyl)triphenylphosphonium bromide With potassium hexamethylsilazane In tetrahydrofuran at -78 - 20℃; for 1h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In tetrahydrofuran at -78℃;	96%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + methyl (triphenylphosphoranylidene)acetate (21204-67-1) → (4S)-1,1-Dimethylethyl 4-<(E)-3'-methoxy-3'-oxo-1'-propenyl>-2,2-dimethyl-3-oxazolidinecarboxylate (129483-65-4)

Conditions	Yield
In benzene Ambient temperature;	95%
In toluene at 0 - 20℃; for 40h;	77%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + ethylamine (75-04-7) → (S)-4-ethylaminomethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1048351-33-2)

Conditions	Yield
Stage #1: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine; ethylamine In methanol at 20℃; for 1.5h; Molecular sieve; Stage #2: With hydrogen; palladium on activated charcoal In methanol at 20℃; under 760.051 Torr;	95%

cycl-isopropylidene malonate (2033-24-1) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (4S)-4-(2,2-dimethyl-4,6-dioxo-[1,3]dioxan-5-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Conditions	Yield
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; L-proline In acetonitrile at 25℃;	95%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + N-ε-(2-Chloro-CBZ)-L-lysine allyl ester hydrochloride (144156-17-2) → (S)-4-{[(S)-1-Allyloxycarbonyl-5-(2-chloro-benzyloxycarbonylamino)-pentylamino]-methyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (144156-07-0)

Conditions	Yield
With sodium cyanoborohydride In methanol for 1h; Ambient temperature;	94%

3-bromofurane (22037-28-1) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → C15H23NO5 (1105713-64-1)

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -78℃;	93%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + sodium chlorodifluoroacetate (1895-39-2) → C12H19F2NO3

Conditions	Yield
With triphenylphosphine In N,N-dimethyl-formamide at 100℃; for 2h; Inert atmosphere;	92.31%

carbon tetrabromide (558-13-4) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (S)-tert-butyl 4-(2,2-dibromovinyl)-2,2-dimethyloxazolidine-3-carboxylate (130418-98-3)

Conditions	Yield
With triphenylphosphine In dichloromethane at 0 - 20℃; for 2.33333h;	92%
Stage #1: carbon tetrabromide With triphenylphosphine In dichloromethane at -30℃; for 0.666667h; Inert atmosphere; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine With triethylamine In dichloromethane at -60 - 0℃; for 2.5h; Inert atmosphere; Stage #3: With sodium hydrogencarbonate In dichloromethane; water	88%
With triphenylphosphine	72%
With triethylamine; triphenylphosphine 1.) CH2Cl2, -20 deg C, 30 min; 2.) CH2Cl2, -60 deg C, 30 min, r.t., overnight; Multistep reaction;
With triethylamine; triphenylphosphine 1) CH2Cl2, -20 deg C, 30 min; 2) CH2Cl2, -60 deg C, 30 min, rt, overnight; Yield given. Multistep reaction;

vinyl magnesium bromide (1826-67-1) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (4R)-4-(1-hydroxy-allyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (768387-35-5)

Conditions	Yield
at -78 - -20℃; for 1.5h;	92%
Addition;	81%
In tetrahydrofuran -78 deg C -> -50 deg C, 2 h;	74%

2,2,4,4-Tetrakis(trifluoromethyl)-1,3-dithietane (791-50-4) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → 2,2-dimethyl-4-(3,3,3-trifluoro-2-trifluoromethyl-propenyl)-oxazolidine-3-carboxylic acid tert-butyl ester (340714-52-5)

Conditions	Yield
With triphenylphosphine In diethyl ether at -78 - 20℃; for 72h; Wittig reaction;	92%
With triphenylphosphine In diethyl ether at -78 - 20℃; for 72h;	92%

tetravinyltin (IV) (1112-56-7) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (1'R,4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4-(1-hydroxy-2-propen-1-yl)-1,3-oxazolidine (114301-35-8) + (4R,1'S)-4-(1-hydroxy-allyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (114301-34-7)

Conditions	Yield
Stage #1: tetravinyltin (IV) With methyllithium In diethyl ether at 0℃; for 0.25h; Inert atmosphere; Stage #2: With zinc dibromide In diethyl ether at 20℃; for 1h; Inert atmosphere; Stage #3: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In diethyl ether at -35 - 20℃; Inert atmosphere;	A 92% B n/a
Stage #1: tetravinyltin (IV) With methyllithium; zinc dibromide In diethyl ether at 20℃; for 1h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In diethyl ether at 20℃; for 2h; Title compound not separated from byproducts;
Stage #1: tetravinyltin (IV) With methyllithium In diethyl ether at 0℃; for 0.25h; Stage #2: With zinc dibromide In diethyl ether at 20℃; for 1h; Stage #3: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine With zinc dibromide In diethyl ether at -78 - 20℃; Title compound not separated from byproducts;

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + (bromomethyl)pentafluorobenzene (1765-40-8) → (S)-2,2-Dimethyl-4-((E)-2-pentafluorophenyl-vinyl)-oxazolidine-3-carboxylic acid tert-butyl ester (752244-60-3)

Conditions	Yield
Stage #1: (bromomethyl)pentafluorobenzene With triphenylphosphine In tetrahydrofuran for 0.25h; Stage #2: With potassium tert-butylate In tetrahydrofuran at 0℃; for 1.5h; Wittig olefination; Stage #3: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In tetrahydrofuran at -78 - 20℃; for 14h; Wittig olefination;	92%

methylmagnesium bromide (75-16-1) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (4R)-(1-hydroxy-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (488727-69-1)

Conditions	Yield
In tetrahydrofuran; diethyl ether at 20℃; for 3h;	91%
In tetrahydrofuran at -78 - 25℃; Inert atmosphere;	77%

tetravinyltin (IV) (1112-56-7) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (4R)-4-(1-hydroxy-allyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (768387-35-5)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide; methyllithium In diethyl ether at -78℃; for 2h;	91%

3,4-dimethoxyphenol (2033-89-8) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → tert-butyl (R)-4-((R)-hydroxy(2-hydroxy-4,5-dimethoxyphenyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate (925703-87-3)

Conditions	Yield
Stage #1: 3,4-dimethoxyphenol With methylmagnesium chloride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In dichloromethane at 0 - 20℃; for 15h;	91%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + 3-chloro-aniline (108-42-9) → (S)-4-[(3-chlorophenylamino)methyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (1048351-01-4)

Conditions	Yield
With sodium cyanoborohydride; zinc(II) chloride In methanol at 20 - 40℃; for 3h; Inert atmosphere;	91%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + ethyl (triphenylphosphoranylidene)acetate (1099-45-2) → (2E',4S)-4-(2'-ethoxycarbonyl-vinyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (134525-18-1, 131713-27-4, 144070-31-5, 149406-02-0)

Conditions	Yield
In tetrahydrofuran for 2.5h; Heating;	90%
In benzene at 20℃; for 36h;	85%
In tetrahydrofuran at 25℃; for 12h; Condensation;	72%

Upstream product

• 108149-60-6 methyl [(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]carboxylate 
• 312-84-5 D-Serine 
• 159846-14-7 methyl (2S)-3-(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)-2-[(tert-butoxy)carbonylamino]propanoate 
• 126645-26-9 (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)propanoate 
• 152491-85-5 (R)-[1-(tert-butyl-dimethyl-silanyloxymethyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester 
• 518986-07-7 (4S)-4-[(t-butyldimethylsilyloxy)methyl]-2,2-dimethyl-3-[(1,1-dimethylethoxy)carbonyl]oxazolidine 
• 136703-59-8 (3S)-3-[(tert-butoxycarbonyl)amino]-4-hydroxybutanoic acid methyl ester 
• 83345-44-2 3-tert-butoxycarbonylamino-4-hydroxy-butyric acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 3262-72-4 (R)-N-tert-butoxycarbonyl serine 
• 108149-63-9 tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 
• 108149-63-9 4-hydroxymethyl-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester 
• 95715-86-9 (S)-2,2-dimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester 4-methyl ester 
• 660852-86-8 (4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid 

Downstream Products

• 133625-87-3 tert-butyl (4S)-2,2-dimethyl-4-vinyl-1,3-oxazolidine-3-carboxylate 
• 204187-63-3 (S)-2,2-Dimethyl-4-[(Z)-2-((2S,3S,4R,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-vinyl]-oxazolidine-3-carboxylic acid tert-butyl ester 
• 204187-65-5 (S)-2,2-Dimethyl-4-[(E)-2-((2S,3S,4R,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-vinyl]-oxazolidine-3-carboxylic acid tert-butyl ester 
• 287962-68-9 (R)-4-[(S)-1-Hydroxy-3-((2R,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-prop-2-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 287962-75-8 (R)-4-[(S)-1-Hydroxy-3-((2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-prop-2-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 287962-69-0 (R)-4-[(S)-1-Hydroxy-3-((2S,3R,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-prop-2-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 287962-70-3 (R)-4-[(S)-1-Hydroxy-3-((2R,3R,4R,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-prop-2-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 287962-71-4 (R)-4-[(S)-1-Hydroxy-3-((2S,3S,4R,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-prop-2-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 287962-73-6 (R)-4-[(S)-3-((2S,3S,4R,5R,6R)-3-Acetylamino-4,5-bis-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-1-hydroxy-prop-2-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 287962-74-7 (R)-4-[(S)-3-((2R,3S,4R,5R,6R)-3-Acetylamino-4,5-bis-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-1-hydroxy-prop-2-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 287962-72-5 (R)-4-[(S)-1-Hydroxy-3-((2R,3S,4R,5S,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-tetrahydro-pyran-2-yl)-prop-2-ynyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 906528-89-0 (R)-tert-butyl 4-((R)-1'-hydroxy-3-phenylprop-2'-ynyl)-2,2-dimethyloxazolidine-3-carboxylate 
• 609812-03-5 tert-butyl (3E,1R,2S)-N-[2-hydroxy-1-(hydroxymethyl)-3-heptadecenyl]-carbamate 
• 368872-48-4 (S)-4-[(E)-2-(2,6-Dibromo-phenylcarbamoyl)-vinyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 

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PYRROLE COMPOUNDS

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

STABLE N-((1R,2R)-1-(2,3-DIHYDROBENZO[B][1,4]DIOXIN-6-YL)-1-HYDROXY-3-(PYRROLIDIN-1-YL)PROPAN-2-YL) OCTANAMIDE (2R,3R)-2,3-DIHYDROXYSUCCINATE PREMIX AND PROCESS FOR PREPARATION THEREOF

The present invention related to stable N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)- 1-hydroxy-3- (pyrrolidin-1-yl)propan-2-yl) octanamide (2R,3R)- 2,3-dihydroxysuccinate premix of formula (Ia) and its process for preparation thereof. The present invention also related to process for the preparation of N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6- yl)-1-hydroxy-3- (pyrrolidin-1-yl) propan-2-yl) octanamide of formula (I) and pharmaceutically acceptable salts.