Borane → 1,1-Dimethylethyl (2S)-4-{[3'-(aminomethyl)-4'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate

HRID 2080310Notes

Reaction equation

HRID 2080310 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16][N:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:19]([CH3:30])[CH2:18]3)[CH:11]=2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].B>C1COCC1>[NH2:2][CH2:1][C:3]1[CH:4]=[C:5]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16][N:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:19]([CH3:30])[CH2:18]3)[CH:11]=2)[CH:6]=[CH:7][C:8]=1[F:9]

Participants

4

Reactant 2

HCID 6331BoraneHCID 577367021,1-Dimethylethyl (2S)-4-[(3'-cyano-4'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

Product 1

HCID 577367151,1-Dimethylethyl (2S)-4-{[3'-(aminomethyl)-4'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylateYield 64.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1,1-dimethylethyl (2S)-4-[(3′-cyano-4′-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate (2.29 g, 5.59 mmol) in THF (50 mL) was flushed with Ar. Borane (19 mL, 1M in THF, 19 mmol) was slowly added and the reaction was allowed to stir at room temperature for 12 hours. The reaction was quenched slowly with water, diluted with water (175 mL) and then extracted with EtOAc (2×250 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The crude residue was placed onto a SPE silica cartridge (20 g) using 50% hexane/50% EtOAc, and then eluted with the following sequence: 50% hexane/50% EtOAc, 10% MeOH/90% DCM, 30% MeOH/70% DCM. The product fractions were combined and concentrated to give the title compound (1.48 g, 64.1%). EI-MS m/z 414(M−H)+.

Workup

  1. customThe reaction was quenched slowly with water
  2. additiondiluted with water (175 mL)
  3. extractionextracted with EtOAc (2×250 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. washeluted with the following sequence
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-5d1074950b94411ab04a2e19c2b6ee33
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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