204254-96-6

Basic information

• Product Name: (1S,5R,6S)-Ethyl 5-(pentan-3-yl-oxy)-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylate
• Synonyms: ETHYL(3R,4S,5S)-4,5-EPOXY-3-(1-ETHYL-PROPOXY)-CYCLOHEX-1-ENE-1-CARBOXYLATE;[1s-(1a,5b,6a)]-5-(1-ethylpropoxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester;(1S,5R,6S)-ETHYL 5-(PENTAN-3-YL-OXY)-7-OXA-BICYCLO[4.1.0]HEPT-3-ENE-3-CARBOXYLATE;ETHYL(3R,4S,5S)-4,5-EPOXY-3-(1-ETHYL-PROPOXY)-CYCLOHEX-1-ENE-1-CARBOXYLATE(INTERMEDIATE OF OSELTAMIVIR PHOSPHATE );ethyl(3R, 4R, 5S)-4,5-epoxy-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid;7-Oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid, 5-(1-ethylpropoxy)-, ethyl ester, (1S,5R,6S)-;-Oxabicyclo[4.1.0]hept-3-ene-3-carboxylicacid,5-(1-ethylpropoxy)-,ethylester,(1S,5R,6S)-;(1S,5R,6S)-5-(1-Ethyl-propoxy)-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester
• CAS NO: 204254-96-6
• Molecular Formula: C₁₄H₂₂O₄
• Molecular Weight: 254.32
• EINECS: 1308068-626-2
• Product Categories: Heterocycles;Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 204254-96-6.mol
• Article Data: 7

Chemical Properties

• Melting Point: 56-57°C
• Boiling Point: 336.495 °C at 760 mmHg
• Flash Point: 145.075 °C
• Appearance: White to off-white solid
• Density: 1.09 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.492
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: (1S,5R,6S)-Ethyl 5-(pentan-3-yl-oxy)-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: (1S,5R,6S)-Ethyl 5-(pentan-3-yl-oxy)-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylate(204254-96-6)
• EPA Substance Registry System: (1S,5R,6S)-Ethyl 5-(pentan-3-yl-oxy)-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylate(204254-96-6)

Safety Data

• Hazardous Substances Data: 204254-96-6(Hazardous Substances Data)

Usage

Chemical Properties

White to Off-White Solid

Uses

An intermediate of Oseltamivir.

InChI:InChI=1/C14H22O4/c1-4-10(5-2)17-11-7-9(14(15)16-6-3)8-12-13(11)18-12/h7,10-13H,4-6,8H2,1-3H3/t11-,12+,13-/m1/s1

Synthetic route

ethyl (3R,4R,5R)-3-(1-ethyl-propoxy)-4-hydroxy-5-methanesulfonyloxycyclohex-1-ene-1-carboxylate (204254-92-2) → (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6)

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 60℃; for 2h;
With potassium hydrogencarbonate In ethanol at 60℃; for 1h;	2 g
With sodium hydrogencarbonate In ethanol at 60 - 65℃; for 1.5h; Inert atmosphere; Industrial scale; Large scale;	1.55 kg

ethyl (3aR,7R,7aR)-2,2-dimethyl-7-methanesulfonyloxy-3a,6,7,7a-tetrahydrobenzo[1,3]dioxole-5-carboxylate (204254-90-0) → (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6)

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate; dimethylsulfide borane complex; potassium hydrogencarbonate 1.) dichloromethane, -20 - -10 deg C, 0.2 h, 2.) ethanol, water, 55-65 deg C, 1 h; Yield given. Multistep reaction;
Stage #1: ethyl (3aR,7R,7aR)-2,2-dimethyl-7-methanesulfonyloxy-3a,6,7,7a-tetrahydrobenzo[1,3]dioxole-5-carboxylate With trimethylsilyl trifluoromethanesulfonate; dimethylsulfide borane complex In dichloromethane at -30 - -20℃; for 1h; Stage #2: With sodium hydrogencarbonate In dichloromethane; water at 20℃; for 12h; Stage #3: With potassium hydrogencarbonate In ethanol; water at 55 - 65℃; for 2h;

ethyl (3aR,7R,7aR)-2,2-dimethyl-7-methanesulfonyloxy-3a,6,7,7a-tetrahydrobenzo[1,3]dioxole-5-carboxylate (204254-84-2) → (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / perchloric acid 2: 1.) BH3-SMe2, trimethylsilyl trifluoromethanesulfonate, 2.) potassium hydroden carbonate / 1.) dichloromethane, -20 - -10 deg C, 0.2 h, 2.) ethanol, water, 55-65 deg C, 1 h View Scheme
Multi-step reaction with 2 steps 1.1: perchloric acid / 18 h 2.1: dimethylsulfide borane complex; trimethylsilyl trifluoromethanesulfonate / dichloromethane / 1 h / -30 - -20 °C 2.2: 12 h / 20 °C 2.3: 2 h / 55 - 65 °C View Scheme

ethyl (3aR,5S,7R,7aR)-5-hydroxy-7-methanesulfonyloxy-2,2-dimethylhexahydrobenzo[1,3]dioxole-5-carboxylate (204254-81-9) → (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: pyridine; sulfuryl dichloride / dichloromethane / -30 - -20 °C 2.1: perchloric acid / 18 h 3.1: dimethylsulfide borane complex; trimethylsilyl trifluoromethanesulfonate / dichloromethane / 1 h / -30 - -20 °C 3.2: 12 h / 20 °C 3.3: 2 h / 55 - 65 °C View Scheme

D-(-)-quinic acid (77-95-2) → (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / acetone / 2 h / Reflux; Large scale 2.1: ethanol / 2 h / 20 °C 2.2: 1 h / 0 - 10 °C 3.1: pyridine; sulfuryl dichloride / dichloromethane / -30 - -20 °C 4.1: perchloric acid / 18 h 5.1: dimethylsulfide borane complex; trimethylsilyl trifluoromethanesulfonate / dichloromethane / 1 h / -30 - -20 °C 5.2: 12 h / 20 °C 5.3: 2 h / 55 - 65 °C View Scheme

2,2-dimethoxy-propane (77-76-9) → (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / acetone / 2 h / Reflux; Large scale 2.1: ethanol / 2 h / 20 °C 2.2: 1 h / 0 - 10 °C 3.1: pyridine; sulfuryl dichloride / dichloromethane / -30 - -20 °C 4.1: perchloric acid / 18 h 5.1: dimethylsulfide borane complex; trimethylsilyl trifluoromethanesulfonate / dichloromethane / 1 h / -30 - -20 °C 5.2: 12 h / 20 °C 5.3: 2 h / 55 - 65 °C View Scheme

(1S,3R,4S,5R)-3,4-O-isopropylidene-1,5-quinic lactone (32384-42-2) → (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: ethanol / 2 h / 20 °C 1.2: 1 h / 0 - 10 °C 2.1: pyridine; sulfuryl dichloride / dichloromethane / -30 - -20 °C 3.1: perchloric acid / 18 h 4.1: dimethylsulfide borane complex; trimethylsilyl trifluoromethanesulfonate / dichloromethane / 1 h / -30 - -20 °C 4.2: 12 h / 20 °C 4.3: 2 h / 55 - 65 °C View Scheme

1-amino-2-propene (107-11-9) + (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl (3R,4S,5R)-5-N-allyllamino-3-(1-ethylpropoxy)-4-hydroxy-1-cyclohexene-1-carboxylate (312904-11-3)

Conditions	Yield
With magnesium bromide In acetonitrile at 55℃; for 16h;	97%

tert-butylamine (75-64-9) + (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → C14H20O3 (1151665-78-9) + C14H23ClO4 + (3R,4S,5R)-[5-(tert-butylamino)-4-hydroxy-3-(pent-3-yloxy)]cyclohex-1-ene-1-carboxylic acid ethyl ester (651324-04-8)

Conditions	Yield
Stage #1: tert-butylamine With magnesium chloride In toluene at 10℃; for 1h; Stage #2: (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester In toluene at 60℃; for 48h; Temperature; Time;	A 1.65% B 0.83% C 95.8%

acetonitrile (75-05-8) + (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (3R,4S,5R)-ethyl 5-acetylamino-4-hydroxy-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate (1443055-47-7)

Conditions	Yield
Stage #1: acetonitrile; (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester With boron trifluoride diethyl etherate at 0℃; for 1.16667h; Stage #2: With water In acetonitrile at 0 - 20℃; for 4h; Stage #3: With potassium carbonate In acetonitrile at 20℃; for 36h; diastereoselective reaction;	95%

tert-butylamine (75-64-9) + (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (3R,4S,5R)-[5-(tert-butylamino)-4-hydroxy-3-(pent-3-yloxy)]cyclohex-1-ene-1-carboxylic acid ethyl ester (651324-04-8)

Conditions	Yield
Stage #1: tert-butylamine; (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester With magnesium chloride In toluene at 50℃; for 23h; Stage #2: With citric acid	91%
Stage #1: tert-butylamine With magnesium chloride In toluene for 6h; Stage #2: (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester In toluene at 25 - 50℃; for 20h;	89.7%

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl-(3R,4S,5R)-5-azido-4-hydroxy-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate

Conditions	Yield
Stage #1: (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester With water; ammonium chloride In ethanol for 0.333333h; Stage #2: With sodium azide In ethanol at 68℃; for 14h;	90%
With sodium azide; ammonium chloride In ethanol; water at 65 - 75℃; for 8h;	86.9%
With sodium azide; ammonium chloride In methanol; water at 65 - 70℃;	70%

benzylamine (100-46-9) + (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl (3R,4S,5R)-5-N-benzylamino-3-(1-ethylpropoxy)-4-hydroxy-1-cyclohexene-1-carboxylate

Conditions	Yield
Stage #1: benzylamine With zinc(II) chloride In tetrahydrofuran for 1h; Stage #2: (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester In tetrahydrofuran at 50℃; for 24h; Reagent/catalyst; Temperature;	89%

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl (3R,4S,5R)-5-amino-3-(1-ethylpropoxy)-4-hydroxy-1-cyclohexene-1-carboxylate (312904-12-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 97 percent / MgBr2*OEt2 / acetonitrile; various solvent(s) / 16 h / 55 °C 2.1: ethanolamine; Pd/C / ethanol / 3 h / Heating 2.2: 77 percent / H2SO4 View Scheme
Multi-step reaction with 2 steps 1.1: zinc(II) chloride / tetrahydrofuran / 1 h 1.2: 24 h / 50 °C 2.1: hydrogen; palladium on activated charcoal / isopropyl alcohol; acetonitrile / 6 h / 60 °C / 760.05 Torr View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl (3R,4R,5S)-5-N-allylamino-4-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate (312904-15-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 97 percent / MgBr2*OEt2 / acetonitrile; various solvent(s) / 16 h / 55 °C 2.1: ethanolamine; Pd/C / ethanol / 3 h / Heating 2.2: 77 percent / H2SO4 3.1: various solvent(s) 4.1: Et3N / various solvent(s) 5.1: various solvent(s) / 15 h / 111 - 112 °C / 2625.21 - 3375.27 Torr View Scheme
Multi-step reaction with 5 steps 1.1: MgBr2*OEt2 / acetonitrile; various solvent(s) / Heating 1.2: H2NCH2CH2OH / Pd/C / ethanol / 3 h / Heating 2.1: 6 h / 100 °C / 750.08 - 3750.38 Torr 3.1: Et3N / ethyl acetate / 0 - 20 °C 4.1: MeSO3H / ethanol / 2.67 h / Heating 5.1: ethyl acetate / 6 h / 112 °C / 750.08 - 4500.45 Torr View Scheme
Multi-step reaction with 5 steps 1.1: MgBr2*OEt2 / acetonitrile; various solvent(s) / Heating 1.2: HOCH2CH2OH / Pd/C / ethanol / Heating 2.1: 6 h / 100 °C / 750.08 - 3750.38 Torr 3.1: Et3N / ethyl acetate / 0 - 20 °C 4.1: MeSO3H / ethanol / 2.67 h / Heating 5.1: ethyl acetate / 6 h / 112 °C / 750.08 - 4500.45 Torr View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl (3R,4S,5R)-5-N-benzylideneamino-3-(1-ethylpropoxy)-4-hydroxy-1-cyclohexene-1-carboxylate (332047-17-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 97 percent / MgBr2*OEt2 / acetonitrile; various solvent(s) / 16 h / 55 °C 2.1: ethanolamine; Pd/C / ethanol / 3 h / Heating 2.2: 77 percent / H2SO4 3.1: various solvent(s) View Scheme
Multi-step reaction with 2 steps 1.1: MgBr2*OEt2 / acetonitrile; various solvent(s) / Heating 1.2: H2NCH2CH2OH / Pd/C / ethanol / 3 h / Heating 2.1: 100 percent / toluene / 0.5 h / 110 °C View Scheme
Multi-step reaction with 2 steps 1.1: MgBr2*OEt2 / acetonitrile; various solvent(s) / Heating 1.2: HOCH2CH2OH / Pd/C / ethanol / Heating 2.1: 100 percent / toluene / 0.5 h / 110 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl (3R,4S,5R)-5-N-benzylideneamino-3-(1-ethylpropoxy)-4-methanesulfonyloxy-1-cyclohexene-1-carboxylate (332047-18-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 97 percent / MgBr2*OEt2 / acetonitrile; various solvent(s) / 16 h / 55 °C 2.1: ethanolamine; Pd/C / ethanol / 3 h / Heating 2.2: 77 percent / H2SO4 3.1: various solvent(s) 4.1: Et3N / various solvent(s) View Scheme
Multi-step reaction with 3 steps 1.1: MgBr2*OEt2 / acetonitrile; various solvent(s) / Heating 1.2: H2NCH2CH2OH / Pd/C / ethanol / 3 h / Heating 2.1: 100 percent / toluene / 0.5 h / 110 °C 3.1: 94 percent / Et3N / ethyl acetate / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: MgBr2*OEt2 / acetonitrile; various solvent(s) / Heating 1.2: HOCH2CH2OH / Pd/C / ethanol / Heating 2.1: 100 percent / toluene / 0.5 h / 110 °C 3.1: 94 percent / Et3N / ethyl acetate / 1 h / 20 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl (3R,4R,5S)-4-N-acetylamino-5-N-allylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate (312904-18-0)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: 97 percent / MgBr2*OEt2 / acetonitrile; various solvent(s) / 16 h / 55 °C 2.1: ethanolamine; Pd/C / ethanol / 3 h / Heating 2.2: 77 percent / H2SO4 3.1: various solvent(s) 4.1: Et3N / various solvent(s) 5.1: various solvent(s) / 15 h / 111 - 112 °C / 2625.21 - 3375.27 Torr 6.1: AcOH; MeSO3H / various solvent(s) / 15 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: MgBr2*OEt2 / acetonitrile; various solvent(s) / Heating 1.2: H2NCH2CH2OH / Pd/C / ethanol / 3 h / Heating 2.1: 6 h / 100 °C / 750.08 - 3750.38 Torr 3.1: Et3N / ethyl acetate / 0 - 20 °C 4.1: MeSO3H / ethanol / 2.67 h / Heating 5.1: ethyl acetate / 6 h / 112 °C / 750.08 - 4500.45 Torr 6.1: AcOH; MeSO3H / various solvent(s) / 0 - 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: MgBr2*OEt2 / acetonitrile; various solvent(s) / Heating 1.2: HOCH2CH2OH / Pd/C / ethanol / Heating 2.1: 6 h / 100 °C / 750.08 - 3750.38 Torr 3.1: Et3N / ethyl acetate / 0 - 20 °C 4.1: MeSO3H / ethanol / 2.67 h / Heating 5.1: ethyl acetate / 6 h / 112 °C / 750.08 - 4500.45 Torr 6.1: AcOH; MeSO3H / various solvent(s) / 0 - 20 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (1R,5R,6R)-{7-(tert-butyl)-5-(pent-3-yloxy)-7-azabicyclo[4.1.0]}hept-3-ene-3-ethyl carboxylate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: MgCl2 / toluene / 23 h / 50 °C 1.2: 91 percent / aq. citric acid 2.1: Et3N / toluene / 5 h / 70 °C 3.1: 93 percent / aq. K2CO3 View Scheme
Multi-step reaction with 2 steps 1.1: magnesium chloride / toluene / 6 h 1.2: 20 h / 25 - 50 °C 2.1: methanesulfonyl chloride / toluene / 1 h / 0 - 10 °C / Inert atmosphere 2.2: 3.5 h / 0 - 70 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (3R,4S,5R)-5-tert-Butylamino-3-(1-ethyl-propoxy)-4-methanesulfonyloxy-cyclohex-1-enecarboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1.1: MgCl2 / toluene / 23 h / 50 °C 1.2: 91 percent / aq. citric acid 2.1: Et3N / toluene / 5 h / 70 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl (3R,4R,5S)-5-N,N-diallylamino-4-(1,1-dimethylethyl)amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate (651324-06-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: MgCl2 / toluene / 23 h / 50 °C 1.2: 91 percent / aq. citric acid 2.1: Et3N / toluene / 5 h / 70 °C 3.1: 93 percent / aq. K2CO3 4.1: 93 percent / PhSO3H / 5 h / 120 °C View Scheme
Multi-step reaction with 3 steps 1.1: magnesium chloride / toluene / 6 h 1.2: 20 h / 25 - 50 °C 2.1: methanesulfonyl chloride / toluene / 1 h / 0 - 10 °C / Inert atmosphere 2.2: 3.5 h / 0 - 70 °C 3.1: benzenesulfonic acid / 5.5 h / 120 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → ethyl (3R,4R,5S)-4-N-acetyl(1,1-dimethylethyl)amino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate (651324-07-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: MgCl2 / toluene / 23 h / 50 °C 1.2: 91 percent / aq. citric acid 2.1: Et3N / toluene / 5 h / 70 °C 3.1: 93 percent / aq. K2CO3 4.1: 93 percent / PhSO3H / 5 h / 120 °C 5.1: 95 percent / NaOAc / 4 h / 116 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (3R,4S,5S)-4-(tert-Butyl-dimethyl-silanyloxy)-5-cyano-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid ethyl ester (382148-62-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / toluene / 20 °C 2: 87 percent / imidasole / dimethylformamide / 20 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (1R,3S,4S,5R)-4-(tert-Butyl-dimethyl-silanyloxy)-3-cyano-5-(1-ethyl-propoxy)-cyclohexanecarboxylic acid ethyl ester (382148-63-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / toluene / 20 °C 2: 87 percent / imidasole / dimethylformamide / 20 °C 3: 91 percent / H2 / Pd/C / ethyl acetate / 2585.81 Torr View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (1R,3R,4S,5R)-4-(tert-Butyl-dimethyl-silanyloxy)-3-(1-ethyl-propoxy)-5-thiocarbamoyl-cyclohexanecarboxylic acid ethyl ester (382148-59-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 85 percent / toluene / 20 °C 2: 87 percent / imidasole / dimethylformamide / 20 °C 3: 91 percent / H2 / Pd/C / ethyl acetate / 2585.81 Torr 4: 73 percent / (TMS)2S; NaOMe / N,N-dimethyl-acetamide / 20 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (1R,3R,4S,5S)-4-(tert-Butyl-dimethyl-silanyloxy)-3-(1-ethyl-propoxy)-5-thiocarbamoyl-cyclohexanecarboxylic acid ethyl ester (382148-64-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 85 percent / toluene / 20 °C 2: 87 percent / imidasole / dimethylformamide / 20 °C 3: 91 percent / H2 / Pd/C / ethyl acetate / 2585.81 Torr 4: 7 percent / (TMS)2S; NaOMe / N,N-dimethyl-acetamide / 20 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (1R,3R,4S,5S)-4-(tert-Butyl-dimethyl-silanyloxy)-3-(1-ethyl-propoxy)-5-(4-phenyl-thiazol-2-yl)-cyclohexanecarboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 5 steps 1: 85 percent / toluene / 20 °C 2: 87 percent / imidasole / dimethylformamide / 20 °C 3: 91 percent / H2 / Pd/C / ethyl acetate / 2585.81 Torr 4: 73 percent / (TMS)2S; NaOMe / N,N-dimethyl-acetamide / 20 °C 5: 9 percent / dimethylformamide / 1 h / 20 °C View Scheme

(1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester (204254-96-6) → (1R,3R,4S,5R)-4-(tert-Butyl-dimethyl-silanyloxy)-3-(1-ethyl-propoxy)-5-(4-phenyl-thiazol-2-yl)-cyclohexanecarboxylic acid ethyl ester

Conditions	Yield
Multi-step reaction with 5 steps 1: 85 percent / toluene / 20 °C 2: 87 percent / imidasole / dimethylformamide / 20 °C 3: 91 percent / H2 / Pd/C / ethyl acetate / 2585.81 Torr 4: 73 percent / (TMS)2S; NaOMe / N,N-dimethyl-acetamide / 20 °C 5: 74 percent / dimethylformamide / 1 h / 20 °C View Scheme

Upstream product

• 949908-55-8 pentan-3-yl 2,2,2-trichloroacetimidate 
• 101769-63-5 (3R,4S,5R)-3,4,5-trihydroxycyclohex-1-ene-1-carboxylic acid ethyl ester 
• 138-59-0 shikimic acid 
• 204254-92-2 ethyl (3R,4R,5R)-3-(1-ethyl-propoxy)-4-hydroxy-5-methanesulfonyloxycyclohex-1-ene-1-carboxylate 
• 204254-84-2 ethyl (3aR,7R,7aR)-2,2-dimethyl-7-methanesulfonyloxy-3a,6,7,7a-tetrahydrobenzo[1,3]dioxole-5-carboxylate 
• 204254-90-0 ethyl (3aR,7R,7aR)-2,2-dimethyl-7-methanesulfonyloxy-3a,6,7,7a-tetrahydrobenzo[1,3]dioxole-5-carboxylate 
• 32384-42-2 (1S,3R,4S,5R)-3,4-O-isopropylidene-1,5-quinic lactone 
• 77-76-9 2,2-dimethoxy-propane 
• 77-95-2 D-(-)-quinic acid 
• 204254-81-9 ethyl (3aR,5S,7R,7aR)-5-hydroxy-7-methanesulfonyloxy-2,2-dimethylhexahydrobenzo[1,3]dioxole-5-carboxylate 

Downstream Products

• 312904-12-4 ethyl (3R,4S,5R)-5-amino-3-(1-ethylpropoxy)-4-hydroxy-1-cyclohexene-1-carboxylate 
• 332047-13-9 ethyl (3R,4R,5S)-4-amino-3-(1-ethylpropoxy)-5-hydroxy-1-cyclohexene-1-carboxylate 
• 312904-11-3 ethyl (3R,4S,5R)-5-N-allyllamino-3-(1-ethylpropoxy)-4-hydroxy-1-cyclohexene-1-carboxylate 
• 651324-04-8 (3R,4S,5R)-[5-(tert-butylamino)-4-hydroxy-3-(pent-3-yloxy)]cyclohex-1-ene-1-carboxylic acid ethyl ester 
• 1362750-72-8 C₁₈H₂₈N₄O₄ 
• 1362750-75-1 C₂₁H₃₇N₂O₄P 
• 1362750-78-4 C₁₈H₃₀N₂O₄ 
• 1362750-47-7 PMC-33 
• 1362750-80-8 C₁₉H₃₅N₂O₄P 
• 1363339-68-7 PMC-34 
• 1362750-86-4 C₁₇H₂₆N₄O₄ 
• 1362750-90-0 C₂₀H₃₅N₂O₄P 
• 1362750-94-4 C₁₇H₂₈N₂O₄ 
• 1362750-99-9 C₂₁H₃₆N₂O₄ 

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