Borane → Phenylmethyl (2S)-4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate

HRID 2080319Notes

Reaction equation

HRID 2080319 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([F:33])=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[C@@H:18]([CH3:32])[CH2:17]3)[CH:10]=2)[CH:8]=1)#[N:2].B>C1COCC1>[NH2:2][CH2:1][C:3]1[CH:4]=[CH:5][C:6]([F:33])=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[C@@H:18]([CH3:32])[CH2:17]3)[CH:10]=2)[CH:8]=1

Participants

4

Reactant 2

HCID 6331BoraneHCID 57730445Phenylmethyl (2S)-4-[(5'-cyano-2'-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate

Product 1

HCID 57730446Phenylmethyl (2S)-4-{[5'-(aminomethyl)-2'-fluoro-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylateYield 92.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of phenylmethyl (2S)-4-[(5′-cyano-2′-fluoro-3-biphenylyl)methyl]-2-methyl-1-piperazinecarboxylate (708 mg, 1.60 mmol) in THF (10 mL) was flushed with Ar. for 15 minutes. Borane (5.6 mL of a 1M solution in THF, 5.6 mmol) was slowly added and the reaction was allowed to stir at room temperature for 12 hours. The reaction was quenched slowly with 1N HCl (1 mL) and allowed to stir for 2 hours at rt. After neutralization to pH>10 with 2N NaOH, the reaction mixture was extracted with EtOAc (2×15 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The crude residue was placed onto a aminopropyl SPE silica cartridge (10 g) and eluted with the following sequence: 50% hexane/50% EtOAc (3×20 mL), 10% MeOH/90% DCM (3×20 mL). The methanol fractions were combined and concentrated to give the title compound (660 mg, 92%). LC/MS: m/z, 448 (M+H), 1.63 min.

Workup

  1. customThe reaction was quenched slowly with 1N HCl (1 mL)
  2. stirringto stir for 2 hours at rt
  3. extractionAfter neutralization to pH>10 with 2N NaOH, the reaction mixture was extracted with EtOAc (2×15 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-7e5fd58e338b4e53a7406c958a8959c7
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

Loading…