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

HRID 18747

Reaction equation

HRID 18747 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:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23][NH2:24]>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:24][CH2:23][C:22]1[CH:25]=[CH:26][CH:27]=[C:20]([F:19])[CH:21]=1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

4

Reactant 2

HCID 668533-FluorobenzylamineHCID 86596330cis-3a,4,5,6,7,7a-Hexahydro-2-methylthio-benzimidazole-1-carboxylic Acid, Tert-Butyl Ester

Product 1

HCID 68569166tert-butyl (3aR,7aS)-2-[(3-fluorophenyl)methylamino]-3a,4,5,6,7,7a-hexahydrobenzimidazole-1-carboxylateYield 73.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of intermediate 76 (200 mg, 0.0.740 mmol), 3-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 188 mg of the product 191. 1H NMR (CDCl3) δ 8.56 (s, 1 H), 7.45-7.20 (m, 3 H), 7.20-6.95 (m, 2 H), 5.20-4.95 (m, 2 H), 4.35-4.10 (m, 2 H), 2.75-2.55 (m, 1 H), 2.20-2.05 (m, 1 H), 1.80-1.05 (m, 15 H); 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-0e53e646914745f6a1fccb3386846b2b
Source dataset
uspto-grants-2010_06
Patent number
US07741493B2

Linked notes

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