Sodium borohydride → 2-[3,5-bis(trifluoromethyl)phenyl]-N-(6-[(7S,9aS)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-[2-(hydroxymethyl)phenyl]-3-pyridinyl}-N,2-dimethylpropanamide

HRID 2074850Notes

Reaction equation

HRID 2074850 reaction equation
[F:1][C:2]([F:54])([F:53])[C:3]1[CH:4]=[C:5]([C:13]([CH3:52])([CH3:51])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:32]3[C@H:41]([CH2:42][O:43][Si:44]([C:47]([CH3:50])([CH3:49])[CH3:48])([CH3:46])[CH3:45])[CH2:40][N:39]4[C@H:34]([CH2:35][O:36][CH2:37][CH2:38]4)[CH2:33]3)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH:30]=[O:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[BH4-].[Na+]>C1COCC1>[F:54][C:2]([F:1])([F:53])[C:3]1[CH:4]=[C:5]([C:13]([CH3:52])([CH3:51])[C:14]([N:16]([C:18]2[CH:19]=[N:20][C:21]([N:32]3[C@H:41]([CH2:42][O:43][Si:44]([C:47]([CH3:48])([CH3:50])[CH3:49])([CH3:45])[CH3:46])[CH2:40][N:39]4[C@H:34]([CH2:35][O:36][CH2:37][CH2:38]4)[CH2:33]3)=[CH:22][C:23]=2[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:30][OH:31])[CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydride2×HCID 592158982-[3,5-bis(trifluoromethyl)phenyl]-N-[6-[(7S,9aS)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-(2-formylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide

Product 1

HCID 592158422-[3,5-bis(trifluoromethyl)phenyl]-N-(6-[(7S,9aS)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-[2-(hydroxymethyl)phenyl]-3-pyridinyl}-N,2-dimethylpropanamideYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[3,5-bis(trifluoromethyl)phenyl]-N-[6-[(7S,9aS)-7-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-4-(2-formylphenyl)-3-pyridinyl]-N,2-dimethylpropanamide (D60, 27.7 mg, 0.0356 mmol) was suspended in dry THF (1.5 mL) before adding sodium borohydride (3 mg, 0.078 mmol) and stirring for 1 hour. Added more sodium borohydride (3 mg, 0.078 mmol) and left stirring for a further 1 and ½ hours. Reaction quenched with water, diluted with EtOAc. Organic layer washed with water, dried (MgSO4). Filtered. Solvent evaporated to afford the title compound as an off white solid in 89% yield. Used crude in the next step.

Workup

  1. waitleft
  2. stirringstirring for a further 1 and ½ hours
  3. customReaction
  4. customquenched with water
  5. additiondiluted with EtOAc
  6. washOrganic layer washed with water
  7. dry with materialdried (MgSO4)
  8. filtrationFiltered
  9. customSolvent evaporated

Sources & evidence

ORD record
ord-e4dc95dde177408d8b6bfd122c342df4
Source dataset
uspto-grants-2011_04
Patent number
US07919491B2

Reaction notes

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