Sodium borohydride → N-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-hydroxybutanamide

HRID 1874274Notes

Reaction equation

HRID 1874274 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@:15]([NH:30][C:31](=[O:36])[CH2:32][C:33](=[O:35])[CH3:34])([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=1.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([C@:15]([NH:30][C:31](=[O:36])[CH2:32][CH:33]([OH:35])[CH3:34])([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)[CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:5]=[C:6]([O:8][C:9]([F:14])([F:13])[CH:10]([F:12])[F:11])[CH:7]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 23582673(R)-N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-oxobutanamide

Product 1

HCID 59458403N-((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-hydroxybutanamideYield 55%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (R)—N-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-oxobutanamide (Example 251, 51 mg, 0.1 mmol), in MeOH (1 mL) was added NaBH4 (10 mL, 0.26 mmol). The reaction mixture was stirred at rt for 1 h and concentrated under reduced pressure. The residue was purified by preparative HPLC (Axia luna column, 30×100 mm, 40-100% MeOH/H2O with 0.1% TFA over 10 min, flow rate 40 mL/min, monitoring at 220 nm) to yield N—((R)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(4-fluorophenyl)-2-phenylethyl)-3-hydroxybutanamide (Example 330) as a pale yellow oil (28 mg, 55% yield). LCMS: RT=2.66 min [M+H] 512.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). 1H NMR (400 MHz, CDCl3) δ ppm 7.13-7.23 (3H, m), 7.02-7.08 (2H, m, J=4.96, 4.56, 4.56, 2.43, 2.43 Hz), 6.96-7.02 (2H, m), 6.85-6.93 (4H, m), 6.67 (2H, d, J=7.07 Hz), 5.87 (1H, t, J=2.78 Hz), 4.10-4.20 (1H, m), 3.95 (1H, dd, J=12.76, 10.74 Hz), 3.73 (1H, dd, J=12.76, 10.74 Hz), 2.32-2.38 (2H, m), 1.22 (3H, d, J=6.32 Hz).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by preparative HPLC (Axia luna column, 30×100 mm, 40-100% MeOH/H2O with 0.1% TFA over 10 min, flow rate 40 mL/min, monitoring at 220 nm)

Sources & evidence

ORD record
ord-40079df5989e4b0d8400468ea907d1c0
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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