4-Fluorobenzylamine → tert-butyl (3aR,7aS)-2-[(4-fluorophenyl)methylamino]-3a,4,5,6,7,7a-hexahydrobenzimidazole-1-carboxylate

HRID 2053541Notes

Reaction equation

HRID 2053541 reaction equation
CS[C:3]1[N:7]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:6]2[CH2:15][CH2:16][CH2:17][CH2:18][C@H:5]2[N:4]=1.[F:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][NH2:25])=[CH:22][CH:21]=1>ClCCl>[C:11]([O:10][C:8]([N:7]1[C@H:6]2[CH2:15][CH2:16][CH2:17][CH2:18][C@H:5]2[N:4]=[C:3]1[NH:25][CH2:24][C:23]1[CH:26]=[CH:27][C:20]([F:19])=[CH:21][CH:22]=1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

4

Reactant 2

HCID 673264-FluorobenzylamineHCID 86596330cis-3a,4,5,6,7,7a-Hexahydro-2-methylthio-benzimidazole-1-carboxylic Acid, Tert-Butyl Ester

Product 1

HCID 68569432tert-butyl (3aR,7aS)-2-[(4-fluorophenyl)methylamino]-3a,4,5,6,7,7a-hexahydrobenzimidazole-1-carboxylateYield 98.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of intermediate 76 (200 mg, 0.0.740 mmol), 4-fluorobenzylamine (0.5 mL, 4.4 mmol) is heated at 100° C. (reaction block) overnight. The reaction mixture is cooled to RT. The reaction mixture is diluted with dichloromethane, washed with 0.1N HCl, and brine. The solvent is evaporated, and the residue triturated with EtOAc, and the insoluble material filtered to give 252 mg of the product 193. 1H NMR (CDCl3) δ 8.55 (s, 1H), 7.55-7.35 (m, 2H), 7.10-7.00 (m, 2H), 5.10-4.90 (m, 2H), 4.30-4.10 (m, 2H), 2.70-2.55 (m, 1H), 2.20-2.05 (m, 1H), 1.80-1.05 (m, 15H); MS: m/z 348 (M++1)

Workup

  1. custom(reaction block) overnight
  2. temperatureThe reaction mixture is cooled to RT
  3. washwashed with 0.1N HCl, and brine
  4. customThe solvent is evaporated
  5. customthe residue triturated with EtOAc
  6. filtrationthe insoluble material filtered

Sources & evidence

ORD record
ord-1baa29cf532f4daa98ff87041fe0656f
Source dataset
uspto-grants-2008_02
Patent number
US07326792B2

Reaction notes

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