Acetyl chloride → HCID 57900286, compound

HRID 1949738Notes

Reaction equation

HRID 1949738 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH3:39])[C:9]([C:11]1[S:38][C:14]2[C:15]3[CH:23]=[CH:22][C:21]([N:24]=C(C4C=CC=CC=4)C4C=CC=CC=4)=[CH:20][C:16]=3[O:17][CH2:18][CH2:19][C:13]=2[CH:12]=1)=[O:10].CC(Cl)=O>CO>[NH2:24][C:21]1[CH:22]=[CH:23][C:15]2[C:14]3[S:38][C:11]([C:9]([N:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])[CH3:39])=[O:10])=[CH:12][C:13]=3[CH2:19][CH2:18][O:17][C:16]=2[CH:20]=1

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 86634843HCID 86634843, compound

Product 1

HCID 57900286HCID 57900286, compoundYield 104.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Solid Pd2(dba)3 (101 mg, 0.11 mmol) and BINAP (205 mg, 0.33 mmol) was added to a 10 mL flask and the whole purged with nitrogen. To the flask was added 8-bromo-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (500 mg, 1.11 mmol), benzophenone imine (303 mg, 1.67 mmol), NaOtBu (213 mg, 2.22 mmol) and toluene (30 mL). The mixture was heated to 80° C. with stirring until the starting material had been consumed (determined by TLC analysis). The mixture was cooled to room temperature, diluted with EtOAc, filtered and concentrated. The crude product was purified by column chromatography (5:1 hexanes:ethyl acetate) to give N-(2-chlorophenyl)-8-(diphenylmethyleneamino)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide as a yellow solid (400 mg, yield 65%). N-(2-chlorophenyl)-8-(diphenylmethyleneamino)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (4.9 g, 8.92 mmol) was dissolved in 10 mL of MeOH. To the solution was added 6 mL of CH3COCl in MeOH (1:10). The mixture was stirred at room temperature for 15 min before concentrated under vacuum. The residue was washed with EtOAc to give 8-amino-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide as a white solid (3.6 g, yield 95%). 1H NMR (MeOD, 400 MHz): δ 7.59-6.60 (m, 8H), 4.21 (t, J=5.2 Hz, 2H), 3.31 (s, 3H), 2.96 (t, J=4.8 Hz, 2H).

Workup

  1. concentrationbefore concentrated under vacuum
  2. washThe residue was washed with EtOAc

Sources & evidence

ORD record
ord-66996fad313e4597b617c55e24bf7fb7
Source dataset
uspto-grants-2013_03
Patent number
US08399690B2

Reaction notes

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