(1,1'-Biphenyl)-3-carboxylic acid, 3'-amino-, methyl ester → (R)-3'-[[2-[[2-(3-Chlorophenyl)-2-[[(tert-butyl)dimethylsilyl]oxy]ethyl][(tert-butoxy)carbonyl]amino]ethyl]amino]-[1,1'-biphenyl]-3-carboxylic acid methyl ester

HRID 1069094Notes

Reaction equation

HRID 1069094 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH2:17])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)=[O:4].[C:18]([O:22][C:23]([N:25]([CH2:43][CH:44]=O)[CH2:26][C@H:27]([O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][CH2:44][CH2:43][N:25]([CH2:26][C@@H:27]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=3)[O:35][Si:36]([C:39]([CH3:40])([CH3:41])[CH3:42])([CH3:38])[CH3:37])[C:23]([O:22][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:24])[CH:12]=2)[CH:8]=[CH:9][CH:10]=1)=[O:4]

Participants

6

Reactant 3

HCID 1394215(1,1'-Biphenyl)-3-carboxylic acid, 3'-amino-, methyl esterHCID 5049666Sodium triacetoxyborohydrideHCID 20666899(R)-[(tert-butoxycarbonyl)-[2-(tertbutyidimethylsilanyloxy)-2-(3-chlorophenyl)ethyl]amino}acetaldehyde

Product 1

HCID 11592646(R)-3'-[[2-[[2-(3-Chlorophenyl)-2-[[(tert-butyl)dimethylsilyl]oxy]ethyl][(tert-butoxy)carbonyl]amino]ethyl]amino]-[1,1'-biphenyl]-3-carboxylic acid methyl esterYield 66.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 3′-amino-[1,1′-biphenyl]-3-carboxylic acid methyl ester (3.0 g) and (R)-[(tert-butoxycarbonyl)-[2-(tertbutyidimethylsilanyloxy)-2-(3-chlorophenyl)ethyl]amino}acetaldehyde (8.2 g) in anhydrous dichloromethane (65 mL) was added acetic acid (8 drops). After stirring for twenty-five minutes, sodium triacetoxyborohydride (5.6 g) was added and the reaction stirred overnight. The reaction was quenched with saturated aqueous sodium bicarbonate and more dichloromethane was added. The organic layer was dried over sodium sulfate and the solvent was removed under reduced pressure to yield a white foam. The residue was purified by silica gel chromatography and eluted with 9:1 hexane:ethyl acetate to provide the title compound as a white foam (5.62 g).

Workup

  1. stirringthe reaction stirred overnight
  2. customThe reaction was quenched with saturated aqueous sodium bicarbonate and more dichloromethane
  3. additionwas added
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customto yield a white foam
  7. customThe residue was purified by silica gel chromatography
  8. washeluted with 9:1 hexane

Sources & evidence

ORD record
ord-89c516ae0e5c435ebf42aa419104312b
Source dataset
uspto-grants-2001_06
Patent number
US06251925B1

Reaction notes

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