160232-08-6

Basic information

• Product Name: tert-Butyl [(1S,2R)-1-Benzyl-2-hydroxy-3-(isobutylamino)propyl]carbamate
• Synonyms: N-[(1S,2R)-2-Hydroxy-3-[(2-methylpropyl)amino]-1-(phenylmethyl)propyl]carbamic Acid 1,1-Dimethylethyl Ester;tert-Butyl [(1S,2R)-1-Benzyl-2-hydroxy-3-(isobutylamino)propyl]carbamate;([1S,2R]-(1-Benzyl-2-hydroxy-3-(isobutyl-amino)propyl)carbamic acid tert-butylester;tert-Butyl ((2S,3R)-3-hydroxy-4-(isobutylamino)-1-phenylbutan-2-yl)carbamate;Carbamicacid,N-[(1S,2R)-2-hydroxy-3-[(2-methylpropyl)amino]-1-(phenylmethyl)propyl]-,1,1-dimethylethyl ester;Fosamprenavir Calcium Intermediates;tert-butyl N-[(2S,3R)-3-hydroxy-4-(2-methylpropylamino)-1-phenylbutan-2-yl]carbamate
• CAS NO: 160232-08-6
• Molecular Formula: C₁₉H₃₂N₂O₃
• Molecular Weight: 336.48
• EINECS: 1533716-785-6
• Product Categories: Aromatics;Chiral Reagents
• Mol File: 160232-08-6.mol
• Article Data: 76

Chemical Properties

• Melting Point: 145 °C
• Boiling Point: 484.697 °C at 760 mmHg
• Flash Point: 246.936 °C
• Appearance: White solid
• Density: 1.04 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.512
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Chloroform, Dichloromethane, Methanol
• PKA: 12.07±0.46(Predicted)
• CAS DataBase Reference: tert-Butyl [(1S,2R)-1-Benzyl-2-hydroxy-3-(isobutylamino)propyl]carbamate(CAS DataBase Reference)
• NIST Chemistry Reference: tert-Butyl [(1S,2R)-1-Benzyl-2-hydroxy-3-(isobutylamino)propyl]carbamate(160232-08-6)
• EPA Substance Registry System: tert-Butyl [(1S,2R)-1-Benzyl-2-hydroxy-3-(isobutylamino)propyl]carbamate(160232-08-6)

Safety Data

• Hazardous Substances Data: 160232-08-6(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

InChI:InChI=1/C19H32N2O3/c1-14(2)12-20-13-17(22)16(11-15-9-7-6-8-10-15)21-18(23)24-19(3,4)5/h6-10,14,16-17,20,22H,11-13H2,1-5H3,(H,21,23)/t16-,17+/m0/s1

Synthetic route

isobutylamine (78-81-9) + (1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester (98760-08-8, 98818-34-9, 98818-35-0, 103127-56-6, 98737-29-2) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
In isopropyl alcohol at 20℃;	100%
In isopropyl alcohol at 60℃; for 6h;	100%
In isopropyl alcohol at 60℃; Inert atmosphere;	100%

isobutylamine (78-81-9) + tert-butyl ((2S,3S)-4-chloro-3-hydroxy-1-phenylbutan-2-yl)carbamate (165727-45-7) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
With potassium hydroxide In ethanol at 15 - 20℃; Large scale;	97.3%
With sodium carbonate In water at 60 - 65℃; for 3h;	105 g
With sodium carbonate In water at 60 - 65℃; for 3h;	105 g

isobutylamine (78-81-9) + (2R,3S)-3-[N-(tert-butyloxycarbonyl)amino]-1,2-epoxy-4-phenylbutane (98760-08-8) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
In isopropyl alcohol at 20 - 30℃; Solvent;	94.67%
In isopropyl alcohol at 80℃; for 2.5h;	93%
In isopropyl alcohol at 80℃; for 2.5h;

isobutyraldehyde (78-84-2) + (1S,2R)-(3-amino-1-benzyl-2-hydroxy-propyl)-carbamic acid tert butyl ester (162536-42-7) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
With sodium tris(acetoxy)borohydride In ethanol at 0 - 20℃; for 5h; Reagent/catalyst;	81.6%
With hydrogen; platinum(IV) oxide In methanol under 7600 Torr; for 2h; Ambient temperature;	80%

isobutylamine (78-81-9) + (2R,3S)-3-[N-(tert-butyloxycarbonyl)amino]-1,2-epoxy-4-phenylbutane (98760-08-8) → tert-butyl [(1S,2R)-1-benzyl-2-hydroxy-3-(isobutylamino)propyl]-N-[(1S,2R)-1-benzyl-2-hydroxypropyl]carbamate + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
In toluene at 20 - 30℃; Solvent;	A n/a B 80%

isobutylamine (78-81-9) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
With 3S-(N-t-butoxycarbonyl)amino-2R-hydroxy-4-phenylbut-1-yl toluenesulfonate In isopropyl alcohol; toluene at 80 - 85℃; for 1.5h;	76.8%

C19H31N3O4 (188404-01-5) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
With hydrogen; nickel In tetrahydrofuran under 760 Torr; Ambient temperature;	64%

2(R)-((tert-butyloxycarbonyl)amino)-1,4-dichloro-3(S)-hydroxybutane (326479-99-6) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: p-TsOH*H2O / CH2Cl2 2.1: NaH / tetrahydrofuran 3.1: CuBr*SMe2 / tetrahydrofuran 4.1: p-TsOH*H2O 4.2: KOH / methanol 5.1: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1: 100 percent / imidazole; DMAP / dimethylformamide / 12 h / 50 °C 2: 100 percent / NaH / tetrahydrofuran / 5 h / 0 °C 3: 75 percent / CuBr*Me2S / toluene; tetrahydrofuran / -78 - -20 °C 4: Bu4NF / tetrahydrofuran 5: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme
Multi-step reaction with 5 steps 1.1: 100 percent / imidazole; DMAP / dimethylformamide / 12 h / 50 °C 2.1: 100 percent / NaH / tetrahydrofuran / 5 h / 0 °C 3.1: 82 percent / Et3N / methanol / 18 h / 20 °C 4.1: TBAF / tetrahydrofuran / 0.67 h / 20 °C 4.2: 75 percent / KOH / methanol / 2 h / 20 °C 5.1: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme

N-t-butyloxycarbonyl-2(S)-(1(S)-t-butyldimethylsilyloxy-2-chloroethyl)aziridine (326480-01-7) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 75 percent / CuBr*Me2S / toluene; tetrahydrofuran / -78 - -20 °C 2: Bu4NF / tetrahydrofuran 3: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1.1: 82 percent / Et3N / methanol / 18 h / 20 °C 2.1: TBAF / tetrahydrofuran / 0.67 h / 20 °C 2.2: 75 percent / KOH / methanol / 2 h / 20 °C 3.1: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme

(S)-2-[(S)-2-Chloro-1-(tetrahydro-pyran-2-yloxy)-ethyl]-aziridine-1-carboxylic acid tert-butyl ester (357604-37-6) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: CuBr*SMe2 / tetrahydrofuran 2.1: p-TsOH*H2O 2.2: KOH / methanol 3.1: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme

2(S)-t-butyldimethylsilyloxy-3(R)-(t-butyloxycarbonyl)amino-1,4-dichlorobutane (326480-00-6) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 100 percent / NaH / tetrahydrofuran / 5 h / 0 °C 2: 75 percent / CuBr*Me2S / toluene; tetrahydrofuran / -78 - -20 °C 3: Bu4NF / tetrahydrofuran 4: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme
Multi-step reaction with 4 steps 1.1: 100 percent / NaH / tetrahydrofuran / 5 h / 0 °C 2.1: 82 percent / Et3N / methanol / 18 h / 20 °C 3.1: TBAF / tetrahydrofuran / 0.67 h / 20 °C 3.2: 75 percent / KOH / methanol / 2 h / 20 °C 4.1: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme

[(1R,2S)-3-Chloro-1-chloromethyl-2-(tetrahydro-pyran-2-yloxy)-propyl]-carbamic acid tert-butyl ester (357604-36-5) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: NaH / tetrahydrofuran 2.1: CuBr*SMe2 / tetrahydrofuran 3.1: p-TsOH*H2O 3.2: KOH / methanol 4.1: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme

[(1S,2S)-1-Benzyl-3-chloro-2-(tetrahydro-pyran-2-yloxy)-propyl]-carbamic acid tert-butyl ester (357604-38-7) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: p-TsOH*H2O 1.2: KOH / methanol 2.1: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme

2(S)-t-butyldimethylsilyloxy-3(S)-(t-butyloxycarbonyl)amino-1-chloro-4-phenylbutane (326480-02-8) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: Bu4NF / tetrahydrofuran 2: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme

(3S)-t-butyldimethylsilyloxy-(2R)-(t-butyloxycarbonyl)amino-4-chloro-1-phenylthiobutane (357604-39-8) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: TBAF / tetrahydrofuran / 0.67 h / 20 °C 1.2: 75 percent / KOH / methanol / 2 h / 20 °C 2.1: 90 percent / propan-2-ol / 5 h / 50 °C View Scheme

(2S,3S)-3-Amino-1-benzyloxy-4-phenyl-butan-2-ol (1053517-88-6) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: CH2Cl2 / 3 h / 23 °C 2: 356 mg / H2 / Pd(OH)2 / ethyl acetate; methanol / 12 h 3: 61 percent / PPh3, DEAD / CHCl3 / 72 h / Heating 4: propan-2-ol / 3.5 h / 68 °C View Scheme

(4S,5S)-4-benzyl-5-benzyloxymethyl-1,3-oxazolidin-2-one (193953-56-9) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 5 steps 1: KOH / ethanol; H2O / 17 h / Heating 2: CH2Cl2 / 3 h / 23 °C 3: 356 mg / H2 / Pd(OH)2 / ethyl acetate; methanol / 12 h 4: 61 percent / PPh3, DEAD / CHCl3 / 72 h / Heating 5: propan-2-ol / 3.5 h / 68 °C View Scheme

((1S,2S)-1-Benzyl-3-benzyloxy-2-hydroxy-propyl)-carbamic acid tert-butyl ester (193953-57-0) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 356 mg / H2 / Pd(OH)2 / ethyl acetate; methanol / 12 h 2: 61 percent / PPh3, DEAD / CHCl3 / 72 h / Heating 3: propan-2-ol / 3.5 h / 68 °C View Scheme

di-tert-butyl dicarbonate (24424-99-5) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: CH2Cl2 / 3 h / 23 °C 2: 356 mg / H2 / Pd(OH)2 / ethyl acetate; methanol / 12 h 3: 61 percent / PPh3, DEAD / CHCl3 / 72 h / Heating 4: propan-2-ol / 3.5 h / 68 °C View Scheme

(2S,3S)-3-(t-butoxycarbonylamino)-4-phenylbutane-1,2-diol (149451-80-9) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 61 percent / PPh3, DEAD / CHCl3 / 72 h / Heating 2: propan-2-ol / 3.5 h / 68 °C View Scheme

N-tert-butoxycarbonyl-L-phenylalanine (13734-34-4) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: 1.) CDI, 2.) t-BuOK / 1.) THF, room temperature, 2 h, 2.) THF, room temperature, 15 h 2: 69 percent / NaBH4 / methanol; tetrahydrofuran / 1 h / 0 °C 3: 89 percent / H2 / Raney Ni / methanol / 17 h / 35 °C / 30400 Torr 4: 80 percent / H2 / PtO2 / methanol / 2 h / 7600 Torr / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1: 1.) CDI, 2.) t-BuOK / 1.) THF, room temperature, 2 h, 2.) THF, room temperature, 15 h 2: NaBH4, TiCl4 / 1,2-dimethoxy-ethane / 1 h / -5 °C 3: 80 percent / H2 / PtO2 / methanol / 2 h / 7600 Torr / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1: triethylamine 2: aluminum sec-butoxide / toluene; 2-methyl-propan-1-ol / 15 - 20 °C / Large scale 3: potassium hydroxide / ethanol / 15 - 20 °C / Large scale View Scheme
Multi-step reaction with 5 steps 1.1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 5 h / 20 °C 2.1: potassium hydroxide / N,N-dimethyl-formamide / 1 h / 10 - 25 °C 2.2: 20 - 25 °C 3.1: aluminum tri-tert-butoxide / isopropyl alcohol / 2 h / 60 - 65 °C 4.1: 5%-palladium/activated carbon; hydrogen / ethanol / 5 h / 30 - 40 °C / 3800.26 Torr 5.1: sodium tris(acetoxy)borohydride / ethanol / 5 h / 0 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: dmap; dicyclohexyl-carbodiimide / dichloromethane / 5 h / 20 °C 2.1: potassium tert-butylate / dimethyl sulfoxide / 1 h / 10 - 25 °C 2.2: 20 - 25 °C 3.1: aluminum tri-tert-butoxide / isopropyl alcohol / 2 h / 60 - 65 °C 4.1: 5%-palladium/activated carbon; hydrogen / ethanol / 5 h / 30 - 40 °C / 3800.26 Torr 5.1: sodium tris(acetoxy)borohydride / ethanol / 5 h / 0 - 20 °C View Scheme

(2S,3R)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane (161282-72-0) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89 percent / H2 / Raney Ni / methanol / 17 h / 35 °C / 30400 Torr 2: 80 percent / H2 / PtO2 / methanol / 2 h / 7600 Torr / Ambient temperature View Scheme

(S)-3-tert-butoxycarbonylamino-1-nitro-4-phenyl-2-butanone (174302-72-8) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 69 percent / NaBH4 / methanol; tetrahydrofuran / 1 h / 0 °C 2: 89 percent / H2 / Raney Ni / methanol / 17 h / 35 °C / 30400 Torr 3: 80 percent / H2 / PtO2 / methanol / 2 h / 7600 Torr / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: NaBH4, TiCl4 / 1,2-dimethoxy-ethane / 1 h / -5 °C 2: 80 percent / H2 / PtO2 / methanol / 2 h / 7600 Torr / Ambient temperature View Scheme
Multi-step reaction with 3 steps 1: aluminum tri-tert-butoxide / isopropyl alcohol / 2 h / 60 - 65 °C 2: 5%-palladium/activated carbon; hydrogen / ethanol / 5 h / 30 - 40 °C / 3800.26 Torr 3: sodium tris(acetoxy)borohydride / ethanol / 5 h / 0 - 20 °C View Scheme

N-nitroso-N-methylisobutylamine (34419-76-6) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 66 percent / LDA / tetrahydrofuran / -78 °C 2: 89 percent / H2 / 20percent Pd(OH)2/C / ethyl acetate / 760 Torr / Ambient temperature 3: 64 percent / H2 / Raney nickel / tetrahydrofuran / 760 Torr / Ambient temperature View Scheme

(2S)-N,N-dibenzylphenylalaninal (123054-12-6, 123808-74-2, 136370-73-5, 111060-64-1) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 66 percent / LDA / tetrahydrofuran / -78 °C 2: 89 percent / H2 / 20percent Pd(OH)2/C / ethyl acetate / 760 Torr / Ambient temperature 3: 64 percent / H2 / Raney nickel / tetrahydrofuran / 760 Torr / Ambient temperature View Scheme
Multi-step reaction with 5 steps 1: lithium / tetrahydrofuran / 3 h / -65 °C / Inert atmosphere 2: palladium hydroxide on carbon; hydrogen / methanol / 4 h / 20 °C / 760.05 Torr 3: triethylamine / tetrahydrofuran / 20 °C / Cooling with ice 4: potassium hydroxide / tetrahydrofuran; methanol / Cooling with ice 5: ethanol / 1 h / 78 °C / Inert atmosphere View Scheme

C28H35N3O2 (188404-00-4) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 89 percent / H2 / 20percent Pd(OH)2/C / ethyl acetate / 760 Torr / Ambient temperature 2: 64 percent / H2 / Raney nickel / tetrahydrofuran / 760 Torr / Ambient temperature View Scheme

isopropylamine (75-31-0) + (1S,2R)-(3-amino-1-benzyl-2-hydroxy-propyl)-carbamic acid tert butyl ester (162536-42-7) → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
In ethanol at 85℃; for 72h;	0.56 g

isobutylamine (78-81-9) + ((R)-1-Oxiranyl-2-phenyl-ethyl)-carbamic acid tert-butyl ester → (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6)

Conditions	Yield
In ethanol for 1h; Heating / reflux;

4-Nitrobenzenesulfonyl chloride (98-74-8) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → [(1S,2R)-3-[(4-nitrophenylsulfonyl)(2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid tert-butyl ester (191226-98-9)

Conditions	Yield
With sodium hydrogencarbonate In dichloromethane; water at 20℃; for 21h;	100%
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 25℃; for 4h;	98.2%
With sodium hydrogencarbonate In dichloromethane; water at 23℃; for 12h;	96%

benzyl chloroformate (501-53-1) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → [(2R,3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-4-phenylbutyl](2-methylpropyl)carbamic acid phenylmethyl ester (160232-10-0)

Conditions	Yield
With triethylamine In dichloromethane at -1.5 - 20℃; for 48h;	100%
Stage #1: benzyl chloroformate; (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol With triethylamine In dichloromethane at -1.5 - 20℃; for 48h; Stage #2: With sodium carbonate In dichloromethane; water for 0.166667h;	100%
With sodium carbonate In tetrahydrofuran at 5 - 10℃; for 3h;	77%

benzothiazole-6-carboxylic acid (3622-35-3) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → tert-butyl (2S,3R)-3-hydroxy-4-(N-isobutylbenzo[d]thiazole-6-carboxamido)-1-phenylbutan-2-ylcarbamate (1160490-14-1)

Conditions	Yield
With triethylamine; HATU In dichloromethane at 20℃;	100%

3-methyl-1H-indazole-5-sulfonyl chloride (869885-64-3) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → {1-benzyl-2-hydroxy-3-[isobutyl-(3-methyl-1H-indazole-5-sulfonyl)-amino]-propyl}-carbamic acid tert-butyl ester (869885-66-5)

Conditions	Yield
With sodium hydrogencarbonate In dichloromethane; water	99%

4-trifluorophenylsulfonyl chloride (2991-42-6) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → tert-butyl ((2S,3R)-3-hydroxy-4-((N-isobutyl-4-(trifluoromethyl)phenyl)sulfonamido)-1-phenylbutan-2-yl)carbamate

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 25℃; for 4h;	98.4%
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Sealed tube;

4-Acetylbenzenesulfonyl chloride (1788-10-9) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → tert-butyl ((2S,3R)-4-((4-acetyl-N-isobutylphenyl)sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carbamate (553644-88-5)

Conditions	Yield
With sodium carbonate In water; ethyl acetate at 20℃; for 18h; Inert atmosphere;	98%
With triethylamine In dichloromethane

(2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → (2R,3S)-3-amino-1-(isobutylamino)-4-phenyl-2-butanol (167011-40-7)

Conditions	Yield
With trifluoroacetic acid In dichloromethane for 5h;	98%

4-methoxy-phenyl-sulphonyl chloride (98-68-0) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → tert-butyl (1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(4-methoxyphenyl)sulfonyl]amino}propylcarbamate (159006-03-8)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 25℃; for 4h;	97.7%
With sodium hydrogencarbonate In dichloromethane; water at 23℃; for 16h;	83%
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 30℃; for 0.5h; Cooling with ice;	82%

1-benzofuran-5-sulfonyl chloride (869885-60-9) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → C27H36N2O6S (1007875-64-0)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 2.5h;	92%
With triethylamine In dichloromethane at 20℃; for 2.5h;	92%
With triethylamine In dichloromethane at 20℃; for 2.5h;	92%
With triethylamine In dichloromethane at 20℃; for 2.5h;	92%

p-acetylaminobenzenesulfonyl chloride (121-60-8) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl-(4-acetylaminobenzenesulfonyl amino)propyl]carbamic acid tert-butyl ester (160230-47-7)

Conditions	Yield
With triethylamine In N,N-dimethyl acetamide at 25 - 35℃; for 2h;	90.56%
With triethylamine In dichloromethane at 0 - 30℃; for 1h; Concentration; Solvent;	86.8%
With sodium hydrogencarbonate In dichloromethane; water for 14h;	714.4 mg
In dichloromethane; water at 10 - 30℃; for 1h; Time;

4-(trifluoro-methoxy)benzene-1-sulfonyl chloride (94108-56-2) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → N-[(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[[(4-trifluoromethoxy)phenyl]sulfonyl]amino]propyl]carbamic acid tert-butyl ester (160232-85-9)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃;	89.7%
With sodium carbonate In dichloromethane at 0 - 20℃;

(4-(chlorosulfonyl)phenyl)methylene diacetate (69232-47-9) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → (acetyloxy)(4-{[{(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}(isobutyl)amino]sulfonyl}phenyl)methyl Acetate (854745-35-0)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 23℃; for 4h;	88%
With triethylamine In tetrahydrofuran at 20℃; for 4h;
With triethylamine In tetrahydrofuran at 25℃; for 4h;
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃;

1-acetyl-2,3-dihydro-1H-indole-5-sulfonyl chloride (52206-05-0) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → ((2S,3R)-4-(1-acetyl-N-isobutylindoline-5-sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carbamate (1393348-48-5)

Conditions	Yield
With sodium hydrogencarbonate In dichloromethane	86%

4-bromobenzenesulfonyl chloride (98-58-8) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → C25H35BrN2O5S

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 16h; Inert atmosphere;	86%

methyl N-[5-(chlorosulfonyl)-1H-benzimidazol-2-yl]carbamate (79213-74-4) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → [(1S,2R)-2-hydroxy-3-[[[2-[(methoxycarbonyl)amino]-1H-benzimidazol-5-yl]sulfonyl]-(2-methylpropyl)amino]-1-(phenylmethyl)propyl]carbamic acid 1,1-dimethylethyl ester

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 5h;	85%

4-(methylsulfanyl)benzenesulfonyl chloride (1129-25-5) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → tert-butyl ((2S,3R)-3-hydroxy-4-((N-isobutyl-4-(methylthio)phenyl)sulfonamido)-1-phenylbutan-2-yl)carbamate

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 25℃;	85%

(4-(chlorosulfonyl)phenyl)boronic acid + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → (4-(N-((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-4-phenylbutyl)-N-isobutylsulfamoyl)phenyl)boronic acid

Conditions	Yield
With triethylamine In dichloromethane at 0 - 23℃; for 1h; Inert atmosphere;	82%

benzo[1,3]dioxol-5-sulfonyl chloride (115010-10-1) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → N-[(1S,2R)-3-[[(benzo-[1,3]-dioxole-5-sulfonyl)](isobutyl)amino]-1-benzyl-2-hydroxypropyl]carbamic acid tert-butyl ester (160233-05-6)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 4h;	81%
With N-ethyl-N,N-diisopropylamine; dmap In tetrahydrofuran at 20℃; for 4h;	81%
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃;	71.2%

(2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) + 6-methoxypyridin-3-ylsulfonyl chloride (312300-42-8) → tert-butyl ((2S,3R)-3-hydroxy-4-((N-isobutyl-6-methoxypyridine)-3-sulfonamido)-1-phenylbutan-2-yl)carbamate

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 25℃;	80%

4-vinylbenzenesulfonyl chloride (2633-67-2) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → tert-butyl ((2S,3R)-3-hydroxy-4-(N-isobutyl-4-vinylphenylsulfonamido)-1-phenylbutan-2-yl)carbamate (854739-70-1)

Conditions	Yield
With sodium carbonate In water; ethyl acetate at 20℃; for 18h; Inert atmosphere;	77%
With triethylamine In dichloromethane at 25℃; for 3h;	54%

(fluorenylmethoxy)carbonyl chloride (28920-43-6) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → C34H42N2O5 (1160051-76-2)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 1h;	76%

3,4-dimethoxybenzene-1-sulfonyl chloride (23095-31-0) + (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol (160232-08-6) → (1S,2R)-{1-benzyl-3-[(3,4-dimethoxybenzenesulfonyl)isobutylamino]-2-hydroxypropyl}carbamic tertbutyl ester

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 0 - 20℃;	65.3%
With sodium hydrogencarbonate In dichloromethane; water for 14h;
With triethylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;

Upstream product

• 78-81-9 isobutylamine 
• 165727-45-7 tert-butyl ((2S,3S)-4-chloro-3-hydroxy-1-phenylbutan-2-yl)carbamate 
• 910642-68-1 C₁₅H₂₀N₃O₃⁽¹⁺⁾ 
• 102123-74-0 (S)-tert-butyl (4-chloro-3-oxo-1-phenylbutan-2-yl)carbamate 
• 64411-37-6 N²-<(tert-butoxy)carbonyl>-L-phenylalanine phenyl ester 
• 7535-56-0 N-t-butoxycarbonyl-L-phenylalanine 4-nitrophenyl ester 
• 98760-08-8 (2R,3S)-3-[N-(tert-butyloxycarbonyl)amino]-1,2-epoxy-4-phenylbutane 
• 188404-01-5 C₁₉H₃₁N₃O₄ 
• 98760-08-8 (1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester 
• 75-64-9 tert-butylamine 
• 75-31-0 isopropylamine 
• 162536-42-7 (1S,2R)-(3-amino-1-benzyl-2-hydroxy-propyl)-carbamic acid tert butyl ester 
• 188404-00-4 C₂₈H₃₅N₃O₂ 
• 123054-12-6 (2S)-N,N-dibenzylphenylalaninal 

Downstream Products

• 191226-98-9 [(1S,2R)-3-[(4-nitrophenylsulfonyl)(2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid tert-butyl ester 
• 553644-88-5 tert-butyl ((2S,3R)-4-((4-acetyl-N-isobutylphenyl)sulfonamido)-3-hydroxy-1-phenylbutan-2-yl)carbamate 
• 854746-19-3 {(1S,2R)-1-Benzyl-3-[(4-chloro-3-nitro-benzenesulfonyl)-isobutyl-amino]-2-hydroxy-propyl}-carbamic acid tert-butyl ester 
• 911067-22-6 {(1S,2R)-1-Benzyl-3-[(4-benzyloxy-benzenesulfonyl)-isobutyl-amino]-2-hydroxy-propyl}-carbamic acid tert-butyl ester 
• 622866-57-3 N-[(1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl[(3-methoxyphenyl)sulfonyl]amino]propyl]carbamic acid tert-butyl ester 
• 186463-23-0 C₂₀H₃₂N₂O₄ 
• 160230-47-7 (1S,2R)-1-benzyl-2-hydroxy-3-[isobutyl-(4-acetylaminobenzenesulfonyl amino)propyl]carbamic acid tert-butyl ester 
• 160232-10-0 [(2R,3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-2-hydroxy-4-phenylbutyl](2-methylpropyl)carbamic acid phenylmethyl ester 
• 183004-96-8 N-[(1S,2R)-3-[(6-benzothiazolylsulfonyl)-(2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamic acid-1,1-dimethylethyl ester 
• 160230-61-5 C₂₇H₃₈FN₃O₆S 
• 475586-13-1 CH₄O₃S*C₂₀H₂₇N₃O₅S 
• 1160490-14-1 tert-butyl (2S,3R)-3-hydroxy-4-(N-isobutylbenzo[d]thiazole-6-carboxamido)-1-phenylbutan-2-ylcarbamate 
• 1309164-70-2 1-ethyl-N-((2S,3R)-3-hydroxy-4-(N-isobutyl-4-nitrophenylsulfonamido)-1-phenylbutan-2-yl)cyclopentanecarboxamide 
• 1309164-51-9 N-((2S,3R)-3-hydroxy-4-(N-isobutyl-4-nitrophenylsulfonamido)-1-phenylbutan-2-yl)-2-((S)-tetrahydrofuran-3-yloxy)acetamide 

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