Sodium triacetoxyborohydride → (S)-(1-{[4,4-Bis-(4-fluoro-phenyl)-butylamino]-methyl}-3-methyl-butyl)-methyl-carbamic acid tert-butyl ester

HRID 990399Notes

Reaction equation

HRID 990399 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH2:9][CH2:10][CH2:11][NH2:12])=[CH:4][CH:3]=1.[C:20]([O:24][C:25](=[O:35])[N:26]([C@H:28]([CH:33]=O)[CH2:29][CH:30]([CH3:32])[CH3:31])[CH3:27])([CH3:23])([CH3:22])[CH3:21].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CCOC(C)=O>[C:20]([O:24][C:25](=[O:35])[N:26]([C@H:28]([CH2:33][NH:12][CH2:11][CH2:10][CH2:9][CH:8]([C:13]1[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=1)[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[CH2:29][CH:30]([CH3:31])[CH3:32])[CH3:27])([CH3:23])([CH3:22])[CH3:21]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 13530069HCID 13530069, compoundHCID 54220075(S)-(1-Formyl-3-methyl-butyl)-methyl-carbamic acid tert-butyl ester

Product 1

HCID 54125409(S)-(1-{[4,4-Bis-(4-fluoro-phenyl)-butylamino]-methyl}-3-methyl-butyl)-methyl-carbamic acid tert-butyl esterYield 70.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

4,4-bis-(4-fluorophenyl)-butylamine (200 mg, 0.77 mmol) was dissolved in CH,2Cl2 (5 mL), treated with (S)-(1-formyl-3-methyl-butyl)-methyl-carbamic acid tert-butyl ester (229 mg, 1.0 mmol), stirred for 30 minutes, then cooled to 0° C., treated with NaBH(OAc)3 (245 mg, 1.16 mmol), and stirred overnight at room temperature. The reaction was diluted with EtOAc (100 mL), washed with saturated bicarbonate solution and brine, dried over Na2SO4, and concentrated. The crude material was chromatographed on silica gel eluting with 4% MeOH/CH2Cl2 to give 257 mg (70%) of the desired product as an oil. MS: 475.4 (M+1 for C28H40N2O2F2); an oil; TLC (SiO2), Rf 0.26 (4% MeOH/CH2Cl2); HPLC (1:1 CH3CN/H2O with 0.1% TFA, C-18 column) 100%, RT=15.013 min.

Workup

  1. stirringstirred overnight at room temperature
  2. washwashed with saturated bicarbonate solution and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude material was chromatographed on silica gel eluting with 4% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-5d77ad6fed0f43758ee948cbb70c46b3
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

Loading…