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

HRID 18748
Notes
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Reaction equation

HRID 18748 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

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, 1 H), 7.55-7.35 (m, 2 H), 7.10-7.00 (m, 2 H), 5.10-4.90 (m, 2 H), 4.30-4.10 (m, 2 H), 2.70-2.55 (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-55c3c36fc7e34f6d9b1a5a99f0ea5893
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07741493B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes