62965-35-9

Basic information

• Product Name: N-Boc-L-tert-Leucine
• Synonyms: BOC-TBU-GLYCINE;BOC-TBU-GLY-OH;BOC-TLE;BOC-TLE-OH;BOC-ALPHA-BUTYLGLYCINE;BOC-ALPHA-T-BUTYLGLYCINE;BOC-ALPHA-T-BUTYLGLYCINE-OH;BOC-ALPHA-T-BUTYL-GLY-OH
• CAS NO: 62965-35-9
• Molecular Formula: C₁₁H₂₁NO₄
• Molecular Weight: 231.29
• EINECS: 1312995-182-4
• Product Categories: Amino Acids;Leucine [Leu, L];Amino Acids & Deriv.;CHIRAL CHEMICALS;Peptide
• Mol File: 62965-35-9.mol
• Article Data: 43

Chemical Properties

• Melting Point: 118-121 °C
• Boiling Point: 350 °C at 760 mmHg
• Flash Point: 165.5 °C
• Appearance: White to slightly yellow/Crystalline Powder
• Density: 1.063 g/cm³
• Vapor Pressure: 7.8E-06mmHg at 25°C
• Storage Temp.: Store at RT.
• Solubility: DMSO (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• BRN: 1962763
• CAS DataBase Reference: N-Boc-L-tert-Leucine(CAS DataBase Reference)
• NIST Chemistry Reference: N-Boc-L-tert-Leucine(62965-35-9)
• EPA Substance Registry System: N-Boc-L-tert-Leucine(62965-35-9)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 62965-35-9(Hazardous Substances Data)

Usage

Chemical Properties

White crystalline powder

Uses

Atazanavir Related Compound A

InChI:InChI=1/C11H21NO4/c1-10(2,3)7(8(13)14)12-9(15)16-11(4,5)6/h7H,1-6H3,(H,12,15)(H,13,14)/p-1/t7-/m1/s1

Synthetic route

L-tert-Leucine (20859-02-3) + di-tert-butyl dicarbonate (24424-99-5) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
With triethylamine In methanol at 0 - 5℃;	100%
With triethylamine In methanol at 0 - 5℃;	100%
With sodium hydroxide In 1,4-dioxane at 20℃; for 12h;	100%

NaHSO4·H2O + L-tert-Leucine (20859-02-3) + di-tert-butyl dicarbonate (24424-99-5) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
With triethylamine In 1,4-dioxane; water	99%
With triethylamine In 1,4-dioxane; water	99%

D,L-N-Boc-t-leucine methyl ester → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + N-Boc-D-tert-leucine methyl ester (153960-35-1)

Conditions	Yield
With Bacillus licheniformis In water at 35℃; for 23h; pH=7.8;	A 93% B n/a
With Bacillus licheniformis In water at 35℃; for 18h; pH=7.8;	A n/a B 82%

N-Boc-L-tert-leucinol (153645-26-2) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; Isopropyl acetate; sodium hydrogencarbonate; sodium bromide at 0 - 25℃;	73%

C14H21F6NO4 → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + (R)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (124655-17-0)

Conditions	Yield
With C28H30N3O2(1+)*Br(1-); sodium hydroxide In chloroform at 0℃; for 24h;	A 52% B n/a

N-(tert-butyloxycarbonyl) azide (1070-19-5) + L-tert-Leucine (20859-02-3) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane

L-tert-Leucine (20859-02-3) + 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile (58632-95-4) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
With triethylamine In 1,4-dioxane; water for 4h; Ambient temperature;

(4S,5R)-3-tert-butoxycarbonyl-4-tert-butyl-5-methoxy-2-oxazolidinone (335628-21-2) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
With potassium hydroxide; potassium permanganate In water; tert-butyl alcohol

D,L-N-Boc-t-leucine methyl ester → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + (R)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (124655-17-0) + N-Boc-D-tert-leucine methyl ester (153960-35-1)

Conditions	Yield
With subtilisin In water at 35℃; for 18h; pH=7.5;

D,L-N-Boc-t-leucine methyl ester → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + N-Boc-D-tert-leucine methyl ester (153960-35-1) + 2-tert-butoxycarbonylamino-3,3-dimethylbutyric acid methyl ester (176504-88-4)

Conditions	Yield
With subtilisin In water at 35℃; for 15h; pH=7.5;

(4S,5R)-4-tert-butyl-5-methoxy-2-oxazolidinone (335627-81-1) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N; DMAP / CH2Cl2 / 2 h / 20 °C 2: KMnO4; KOH / 2-methyl-propan-2-ol; H2O View Scheme

di-tert-butyl dicarbonate (24424-99-5) + tert-butylaminoacetic acid (58482-93-2) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
In tetrahydrofuran; sodium hydroxide

t-butoxycarbonyl-anhydride + L-tert-Leucine (20859-02-3) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In 1,4-dioxane; water; ethyl acetate

(S)-ethyl 3,3-dimethyl-2-[(S)-phenylmethanesulfinamido]butanoate (1203546-60-4) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride / methanol 2: triethylamine 3: lithium hydroxide / water View Scheme

(E)-[(S)-2-methylpropane-2-sulfinylimino]acetic acid ethyl ester → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: tetrahydrofuran / 12 h / -20 - 20 °C / Inert atmosphere 2: hydrogenchloride / methanol 3: triethylamine 4: lithium hydroxide / water View Scheme

C13H25NO4 (1465120-76-6) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
With lithium hydroxide In water

di-tert-butyl dicarbonate (24424-99-5) + ethyl (S)-2-amino-3,3-dimethylbutanoate (69557-34-2) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine 2: lithium hydroxide / water View Scheme

(S)-ethyl 2-[butanesulfinamido]-3,3-dimethylbutanoate → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / methanol 2: triethylamine 3: lithium hydroxide / water View Scheme

(R)-1-chloro-3,3-dimethyl-2-butanol (152488-38-5) → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: di-isopropyl azodicarboxylate; triphenylphosphine / toluene / 15 h / -5 - 5 °C / Heating 2: hydrogenchloride; water / 15 h / Reflux 3: sodium hydroxide / water; ethanol / 40 - 50 °C 4: sodium hydrogencarbonate; sodium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; Isopropyl acetate; sodium hypochlorite / 0 - 25 °C View Scheme

C10H16ClNO2 → N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: hydrogenchloride; water / 15 h / Reflux 2: sodium hydroxide / water; ethanol / 40 - 50 °C 3: sodium hydrogencarbonate; sodium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; Isopropyl acetate; sodium hypochlorite / 0 - 25 °C View Scheme

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → (S)-tert-butyl (1-amino-3,3-dimethyl-1-oxobutan-2-yl)carbamate (372199-21-8)

Conditions	Yield
With ammonium chloride; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h;	100%
With 4-methyl-morpholine; ammonium chloride; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran at -20℃; for 0.5h; Stage #2: With ammonium hydroxide In tetrahydrofuran at -20 - 20℃;
With pyridine; di-tert-butyl dicarbonate; ammonium bicarbonate

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + L-4-hydroxyproline methyl ester hydrochloride (40216-83-9) → (2S,4R)-methyl 1-{(S)-2-[(tert-butoxycarbonyl)amino]-3,3-dimethylbutanoyl}-4-hydroxypyrrolidine-2-carboxylate (630421-45-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 0 - 20℃;	100%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	98%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h;	92%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + benzyl bromide (100-39-0) → (S)-benzyl 2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (154092-61-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 72h;	100%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 22℃; for 3.5h;	98%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; for 3.08333h;	93%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 72h;

4R-(7-methoxy-2-pyrazol-1-yl-quinolin-4-yloxy)-pyrrolidine-2S-carboxylic acid methyl ester hydrochloride (918662-07-4) + N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → 1-(2S-tert-butoxycarbonylamino-3,3-dimethylbutyryl)-4R-(7-methoxy-2-pyrazol-1-yl-quinolin-4-yloxy)-pyrrolidine-2S-carboxylic acid methyl ester (918662-09-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane; N,N-dimethyl-formamide at 20℃; for 16h;	100%

4R-(5-chloropyridin-2-yloxy)-pyrrolidine-2S-carboxylic acid methyl ester hydrochloride salt + N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → 1-(2S-tert-butoxycarbonylamino-3,3-dimethylbutyryl)-4R-(5-chloropyridin-2-yloxy)-pyrrolidine-2S-carboxylic acid methyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane; N,N-dimethyl-formamide at 20℃; for 16h;	100%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + methyl iodide (74-88-4) → methyl (2S)-3,3-Dimethyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoate (287210-99-5)

Conditions	Yield
With silver(l) oxide In N,N-dimethyl-formamide at 45℃; Inert atmosphere;	100%
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 8h;	89%
With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃;

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + N,N-dimethylammonium chloride (506-59-2) → (S)-tert-butyl 1-(dimethylamino)-3,3-dimethyl-1-oxobutan-2-ylcarbamate (340161-34-4)

Conditions	Yield
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine With HBTU In dichloromethane for 0.0333333h; Inert atmosphere; Stage #2: N,N-dimethylammonium chloride With N-ethyl-N,N-diisopropylamine In dichloromethane for 1.5h; Inert atmosphere;	100%
With triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h; Cooling with ice;	91%
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 3h;

(R)-3-[(2S,3S)-2-amino-3-phenylbutyrylamino]-3-(thiazol-2-yl)propanoic acid methyl ester (66854-34-0) + N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → N-{N'-tert-butoxycarbonyl-L-tert-leucyl-[(3S)-3-methyl-L-phenylalanyl]}-3-amino-3-(thiazol-2-yl)propanoic acid methyl ester (1138161-59-7)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃;	100%
With N-ethyl-N,N-diisopropylamine; O-(benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate In dichloromethane; N,N-dimethyl-formamide	100%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + 1,2-diamino-benzene (95-54-5) → N-tert-butoxycarbonyl-L-tert-leucine 2-aminoanilide (1138161-53-1)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃;	100%

4-nitro-benzoic acid 5-(1-methoxycarbonyl-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl ester hydrochloride + N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → C30H40N4O10 (1219511-19-9)

Conditions

Yield

Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 20℃; for 0.166667h; Stage #2: 4-nitro-benzoic acid 5-(1-methoxycarbonyl-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl ester hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane for 15h; Stage #3: N-tert-butyloxycarbonyl-L-tert-leucine With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane for 5h;

100%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + (S)-methyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate → (S)-methyl 2-((S)-2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoyl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylate

Conditions	Yield
With 4-methyl-morpholine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; Inert atmosphere;	100%
With 4-methyl-morpholine; 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃;

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + para-bromophenacyl bromide (99-73-0) → (S)-2-(4-bromophenyl)-2-oxoethyl 2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 2h; Cooling with ice;	100%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + benzyl alcohol (100-51-6) → (S)-benzyl 2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (154092-61-2)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 12h;	99%
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine With 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile; triethylamine In 1,4-dioxane Stage #2: benzyl alcohol With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 0℃;
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 0℃;

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + methylamine (74-89-5) → (S)-(2,2-dimethyl-1-methylcarbamoylpropyl)carbamic acid tert-butyl ester (200865-04-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In DMF (N,N-dimethyl-formamide) at 0 - 20℃; for 4h;	99%
Stage #1: methylamine With 1-hydroxy-pyrrolidine-2,5-dione In methanol; N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: N-tert-butyloxycarbonyl-L-tert-leucine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In methanol; N,N-dimethyl-formamide at 0 - 20℃; for 3h;
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 23℃; for 18h; Inert atmosphere;
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere;

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + benzylamine (100-46-9) → (S)-2-amino-N-benzyl-3,3-dimethylbutanamide (207121-91-3)

Conditions	Yield
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine; benzylamine With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane for 1.5h; Stage #2: With trifluoroacetic acid In dichloromethane at 20℃; for 1h; Further stages.;	99%
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine; benzylamine With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 23℃; for 2h; Stage #2: With trifluoroacetic acid In dichloromethane at 23℃; for 1h; Further stages.;	98%
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.0333333h; Sealed tube; Stage #2: benzylamine With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Sealed tube; Stage #3: With trifluoroacetic acid In dichloromethane at 20℃; for 1h; Sealed tube;

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + (R)-4-hydroxy-L-proline ethyl ester (1499-56-5) → (2S,4R)-methyl 1-{(S)-2-[(tert-butoxycarbonyl)amino]-3,3-dimethylbutanoyl}-4-hydroxypyrrolidine-2-carboxylate (630421-45-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 20℃; for 12h;	99%
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 0 - 20℃; for 12h;	99%
With 4-methyl-morpholine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; tert-butyl alcohol In dichloromethane at 20℃;	60%
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 0 - 20℃; for 18h;
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine With HATU In dichloromethane at 20℃; for 0.25h; Stage #2: (R)-4-hydroxy-L-proline ethyl ester With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 15h;

2-(1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester (630424-24-7) + N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → BocNH-(L-t-BuGly)-[(4R)-[2-(2-isopropylaminothiazol-4-yl)-7-methoxyquinoline-4-oxo]-S-proline]-(1R,2S-vinyl acca)-COOEt (630424-25-8)

Conditions	Yield
Stage #1: 2-(1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester With hydrogenchloride In 1,4-dioxane for 2.5h; Stage #2: N-tert-butyloxycarbonyl-L-tert-leucine With 4-methyl-morpholine; HATU In DMF (N,N-dimethyl-formamide)	99%
Stage #1: 2-(1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-pyrrolidine-1-carboxylic acid tert-butyl ester With hydrogenchloride In 1,4-dioxane for 2.5h; Stage #2: N-tert-butyloxycarbonyl-L-tert-leucine With 4-methyl-morpholine; HATU In N,N-dimethyl-formamide	99%

(2S,4R)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)-4-(7-methoxy-2-phenylquinolin-4-yloxy)pyrrolidine-2-carboxamide dihydrochloride + N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → tert-butyl ((S)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-((7-methoxy-2-phenylquinolin-4-yl)oxy)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)carbamate (445304-34-7)

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h; Product distribution / selectivity;	99%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + N-(diphenylmethyl)methylamine (14683-47-7) → tert-butyl (S)-{1-[benzhydryl(methyl)amino]-3,3-dimethyl-1-oxobutan-2-yl}carbamate (1200405-67-9)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 72h; Inert atmosphere;	99%
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 72h;	91%
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere;

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + (2S,4R)-4-hydroxy-N-{ [4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}pyrrolidine-2-carboxamide hydrochloride (1448189-90-9) → tert‐butyl N‐[(2S)‐1‐[(2S,4R)‐4‐hydroxy‐2‐({[4‐(4‐methyl‐1,3‐thiazol‐5‐yl)phenyl]methyl}carbamoyl)pyrrolidin‐1‐yl]‐3,3‐dimethyl‐1‐oxobutan‐2‐yl]carbamate (1448189-98-7)

Conditions	Yield
With triethylamine; HATU In N,N-dimethyl-formamide at 20℃; for 2h;	99%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 16h;	84.46%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 0 - 20℃; for 12h; Inert atmosphere;	70%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + [(3R,5S)-5-[[4-[4-[[2-[2-(cyclopropylmethylamino)-4-pyridyl]oxazole-4-carbonyl]amino]-3-(difluoromethyl)pyrazol-1-yl]phenyl]methylcarbamoyl]pyrrolidin-3-yl]acetate → [(3R,5S)-1-[(2S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoyl]-5-[[4-[4-[[2-[2-(cyclopropylmethylamino)-4-pyridyl]oxazole-4-carbonyl] amino]-3-(difluoromethyl)pyrazol-1-yl]phenyl]methylcarbamoyl]pyrrolidin-3-yl]acetate

Conditions

Yield

Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine; [(3R,5S)-5-[[4-[4-[[2-[2-(cyclopropylmethylamino)-4-pyridyl]oxazole-4-carbonyl]amino]-3-(difluoromethyl)pyrazol-1-yl]phenyl]methylcarbamoyl]pyrrolidin-3-yl]acetate With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h;

99%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + benzyl-methyl-amine (103-67-3) → tert-butyl (S)-1-(N-benzyl-N-methylcarbamoyl)-2,2-dimethylpropylcarbamate (1032509-62-8)

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 23℃; for 18h; Inert atmosphere;	98%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 23℃; for 18h; Inert atmosphere;	98%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h;	97%

C2HF3O2*C14H21N3O5S (630422-57-0) + N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → BOC-NH-(L-tert-BuGly)-[(4R)-hydroxy-S-proline]-(1R,2S-vinyl acca)-CONHSO2-cyclopropane (630419-17-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 20℃; for 48h;	98%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + (2S,4R)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide trifluoroacetic acid → tert‐butyl N‐[(2S)‐1‐[(2S,4R)‐4‐hydroxy‐2‐({[4‐(4‐methyl‐1,3‐thiazol‐5‐yl)phenyl]methyl}carbamoyl)pyrrolidin‐1‐yl]‐3,3‐dimethyl‐1‐oxobutan‐2‐yl]carbamate (1448189-98-7)

Conditions	Yield
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine; (2S,4R)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide trifluoroacetic acid With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Stage #2: With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h;	98%
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h;	98%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + (S)-7-nitro-N-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide → tert-butyl ((S)-3,3-dimethyl-1-((S)-7-nitro-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-1-oxobutan-2-yl)carbamate

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	98%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + 4-fluoro-2-methoxyaniline (450-91-9) → tert-butyl (S)-(1-((4-fluoro-2-methoxyphenyl)amino)-3,3-dimethyl-1-oxobutan-2-yl)carbamate

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 0 - 20℃; for 12h; Inert atmosphere;	98%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + isobutyl chloroformate (543-27-1) → (S)-tert-butyl (1-amino-3,3-dimethyl-1-oxobutan-2-yl)carbamate (372199-21-8)

Conditions	Yield
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine; isobutyl chloroformate at 0℃; for 0.5h; Stage #2: With ammonium hydroxide In water at 20℃; for 1.5h;	98%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → L-tert-Leucine (20859-02-3)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane	97%
Stage #1: N-tert-butyloxycarbonyl-L-tert-leucine With methanesulfonic acid In dichloromethane at 25℃; for 3h; Stage #2: With triethylamine In dichloromethane at 25℃; for 1h;	75%
With hydrogenchloride In water; toluene at 60℃; for 3h;

Upstream product

• 1070-19-5 N-(tert-butyloxycarbonyl) azide 
• 20859-02-3 L-tert-Leucine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 58482-93-2 tert-butylaminoacetic acid 
• 153645-26-2 N-Boc-L-tert-leucinol 
• 152488-38-5 (R)-1-chloro-3,3-dimethyl-2-butanol 
• 69557-34-2 ethyl (S)-2-amino-3,3-dimethylbutanoate 
• 1465120-76-6 C₁₃H₂₅NO₄ 
• 1203546-60-4 (S)-ethyl 3,3-dimethyl-2-[(S)-phenylmethanesulfinamido]butanoate 
• 335627-81-1 (4S,5R)-4-tert-butyl-5-methoxy-2-oxazolidinone 
• 335628-21-2 (4S,5R)-3-tert-butoxycarbonyl-4-tert-butyl-5-methoxy-2-oxazolidinone 
• 58632-95-4 2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile 

Downstream Products

• 1026356-78-4 {(S)-1-[(S)-2-Cyclohexyl-1-((2S,4R)-4-methyl-5-oxo-tetrahydro-furan-2-yl)-ethylcarbamoyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester 
• 198956-55-7 {1-[(S)-2-((S)-2-tert-Butoxycarbonylamino-3,3-dimethyl-butyrylamino)-3-dimethylcarbamoyl-propionylamino]-ethyl}-phosphonic acid diphenyl ester 
• 198956-38-6 {(S)-1-[(S)-1-((S)-3-Benzylcarbamoyl-3,3-difluoro-2-hydroxy-1-methyl-propylcarbamoyl)-2-dimethylcarbamoyl-ethylcarbamoyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester 
• 337363-02-7 (S_S)-N-(N-tert-Butyloxycarbonyl-L-tert-leucinyl)-S-methyl S-phenyl sulfoximine 
• 305129-78-6 (R)-N-tert-butyl-3-[(2S,3S)-3-[(S)-2-(tert-butoxycarbonyl)amino-3,3-dimethylbutanoyl]amino-2-hydroxy-4-phenylbutanoyl]-1,3-thiazolidine-4-carboxamide 
• 340166-80-5 (S)-N-benzyl 2-(N'-t-butoxycarbonylamino)-3,3-dimethylbutanamide 
• 164514-61-8 {1-[1-benzyl-2-hydroxy-3-[1-(2-hydroxy-4-methoxy-benzylcarbamoyl)-2-methyl-propylcarbamoyl]-3-(4-methoxy-benzylamino)-propylcarbamoyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester 
• 374783-12-7 N-t-butoxycarbonyl-L-t-butylglycine p-nitrophenyl ester 
• 187345-37-5 ethyl (S,E)-4-((S)-2-((tert-butoxycarbonyl)amino)-N,3,3-trimethylbutanamido)-2,5-dimethylhex-2-enoate 
• 176504-88-4 2-tert-butoxycarbonylamino-3,3-dimethylbutyric acid methyl ester 
• 479423-20-6 N-((1R,2R)-2-NH₂-cyclohexyl)-N'-((S)-CH(t-Bu)CONHBn)thiourea 
• 479423-19-3 (2S)-N-benzyl-2-isothiocyanato-3,3-dimethylbutanamide 

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