Methyl (4-fluoro-3-nitrophenyl)carbamate → Methyl (4-{[(4,4-difluorocyclohexyl)methyl]amino}-3-nitrophenyl)carbamate

HRID 1987195Notes

Reaction equation

HRID 1987195 reaction equation
Cl.[F:2][C:3]1([F:11])[CH2:8][CH2:7][CH:6]([CH2:9][NH2:10])[CH2:5][CH2:4]1.F[C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:23])[O:21][CH3:22])=[CH:15][C:14]=1[N+:24]([O-:26])=[O:25]>CCO>[F:2][C:3]1([F:11])[CH2:8][CH2:7][CH:6]([CH2:9][NH:10][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:23])[O:21][CH3:22])=[CH:15][C:14]=2[N+:24]([O-:26])=[O:25])[CH2:5][CH2:4]1

Participants

4

Reactant 2

HCID 3636899Methyl (4-fluoro-3-nitrophenyl)carbamateHCID 451589311-(4,4-Difluorocyclohexyl)methanamine hydrochloride

Product 1

HCID 57723212Methyl (4-{[(4,4-difluorocyclohexyl)methyl]amino}-3-nitrophenyl)carbamate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Following the same procedure as in Step C of Example 1 using [(4,4-difluorocyclohexyl)methyl]amine hydrochloride (210 mg, 1.12 mmol), methyl (4-fluoro-3-nitrophenyl)carbamate (200 mg, 0.934 mmol) and TEA (0.390 mL, 2.80 mmol) in 10 mL of EtOH. The crude product was purified by silica gel flash chromatography using 5% ether/DCM as eluent. Yield: 200 mg (62%). 1H NMR (400 MHz, CHLOROFORM-D): δ 1.34-1.47 (m, 2 H), 1.65-1.75 (m, 2 H), 1.78-1.85 (m, 1 H), 1.90-1.93 (m, 1 H), 1.94-1.97 (m, 1 H), 2.10-2.21 (m, 2 H), 3.23 (dd, J=6.64, 5.66 Hz, 2 H), 3.78 (s, 3 H), 6.48 (br.s, 1 H), 6.83 (d, J=9.18 Hz, 1 H), 7.66 (br.s, 1 H), 8.05 (br.s, 1 H), 8.07 (d, J=2.54 Hz, 1 H).

Workup

  1. customThe crude product was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-aa8026339ff84ec4829a1c928511065e
Source dataset
uspto-grants-2009_06
Patent number
US07550495B2

Reaction notes

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