Sodium borohydride → tert-butyl 3-methoxybenzyl((2R,3S)-3-(3-(benzamido)-5-(1-hydroxyethyl)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate

HRID 1454188Notes

Reaction equation

HRID 1454188 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:49]=[CH:50][CH:51]=1)[CH2:6][N:7]([CH2:15][C@@H:16]([OH:48])[C@@H:17]([NH:27][C:28](=[O:47])[C:29]1[CH:34]=[C:33]([NH:35][C:36](=[O:43])[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:32]=[C:31]([C:44](=[O:46])[CH3:45])[CH:30]=1)[CH2:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=1)[C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11].[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:49]=[CH:50][CH:51]=1)[CH2:6][N:7]([CH2:15][C@@H:16]([OH:48])[C@@H:17]([NH:27][C:28](=[O:47])[C:29]1[CH:30]=[C:31]([CH:44]([OH:46])[CH3:45])[CH:32]=[C:33]([NH:35][C:36](=[O:43])[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:34]=1)[CH2:18][C:19]1[CH:20]=[C:21]([F:26])[CH:22]=[C:23]([F:25])[CH:24]=1)[C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:12])[CH3:13]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 68827142tert-Butyl 3-methoxybenzyl((2R,3S)-3-(3-acetyl-5-(benzamido)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate

Product 1

HCID 68828010tert-butyl 3-methoxybenzyl((2R,3S)-3-(3-(benzamido)-5-(1-hydroxyethyl)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamateYield 75.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

tert-Butyl 3-methoxybenzyl((2R,3S)-3-(3-acetyl-5-(benzamido)benzamido)-4-(3,5-difluorophenyl)-2-hydroxybutyl)carbamate (20 mg, 0.0282 mmol) was dissolved in MeOH (0.2 mL) and sodium borohydride (1.43 mg, 0.0378 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated and partitioned between ethyl acetate and H2O. The organic layer was separated and purified by reverse phase prep HPLC to give the title compound (15 mg): 1H NMR (CD3OD, 500 MHz) δ ppm 0.71 (3H, t, J=5 Hz), 1.02 (3H, m), 1.45-1.47 (2H, m), 1.54 (2H, m), 1.74 (2H, m), 2.85 (1H, m), 3.09-3.18 (3H, m), 3.28 (1H, m), 3.49 (2H, m), 3.72-3.81 (4H, m), 3.97 (1H, m), 4.29 (1H, m), 4.41-4.44 (1H, m), 4.75 (1H, m), 4.90 (1H, m), 6.71 (1H, m), 6.81-6.82 (3H, m), 6.89 (2H, m), 7.22 (1H, m), 7.49-7.52 (2H, m), 7.76 (1H, m). HPLC retention time: 2.223 min (method A). MS (ESI) (M+H)+ 712.57.

Workup

  1. concentrationThe mixture was concentrated
  2. custompartitioned between ethyl acetate and H2O
  3. customThe organic layer was separated
  4. custompurified by reverse phase prep HPLC

Sources & evidence

ORD record
ord-aa90d17310c244009118ecac48bac818
Source dataset
uspto-grants-2009_01
Patent number
US07476764B2

Reaction notes

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