Formic Acid → HCID 22676775, compound

HRID 1006288Notes

Reaction equation

HRID 1006288 reaction equation
C(O)=O.[CH:4]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[N:17]([CH2:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[C:16]=3[C:32]([O:34]C(C)(C)C)=[O:33])[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5]1>ClCCl>[CH:4]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[N:17]([CH2:24][C:25]4[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=4)[C:16]=3[C:32]([OH:34])=[O:33])[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5]1

Participants

4

Reactant 2

HCID 284Formic AcidHCID 22676784HCID 22676784, compound

Product 1

HCID 22676775HCID 22676775, compoundYield 85.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Formic acid (4 mL) was added dropwise to a stirred solution of tert-Butyl 3-[3-(cyclopropylmethoxy)phenyl]-1-[(4-fluorophenyl)methyl]indole-2-carboxylate (Example 72, 431 mg, 0.91 mmol) in dichloromethane (1.0 mL). The reaction was stirred at room temperature for 8 h, then concentrated in vacuo. The resulting solids were placed on a pad of silica gel and purified by chromatography (gradient from 30% ethyl acetate/hexane to 100% ethyl acetate) to afford 3-[3-(cyclopropylmethoxy)phenyl]-1-[(4-fluorophenyl)methyl]indole-2-carboxylic acid (324 mg, 85%): mp=200-202° C., 1H NMR acetone-d6) 0.32-0.37 (m, 2 H), 0.55-0.61 (m, 2 H), 1.21-1.31 (m, 1 H), 3.86 (d, J=7.0 Hz, 2 H), 5.90 (s, 2 H), 6.89-6.93 (m, 1 H), 7.00-7.08 (m, 4 H), 7.11-7.16 (m, 2 H), 7.18-7.24 (m, 2 H), 7.30-7.36 (m, 2 H), 7.52-7.58 (m, 2 H), 11.28 (br s, 1 H); mass spectroscopy gave MH+=416 (60%).

Workup

  1. concentrationconcentrated in vacuo
  2. custompurified by chromatography (gradient from 30% ethyl acetate/hexane to 100% ethyl acetate)

Sources & evidence

ORD record
ord-2e938b1892204333bb7a46542d1c0621
Source dataset
uspto-grants-2004_09
Patent number
US06787651B2

Reaction notes

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