Methanol → HCID 19736602, compound

HRID 326281Notes

Reaction equation

HRID 326281 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=O)=[C:4]([NH:12][C:13](=[O:20])[CH2:14][C:15]2[CH:19]=[CH:18][S:17][CH:16]=2)[CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].C1(C)C=CC=CC=1.CO>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:6](=[O:8])[CH:14]([C:15]3[CH:19]=[CH:18][S:17][CH:16]=3)[C:13](=[O:20])[NH:12]2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 1140TolueneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 67794781HCID 67794781, compound

Product 1

HCID 19736602HCID 19736602, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of thiophene-3-acetic acid (1.4 g, 10 mmol) in dichloromethane (40 ml) was added oxalyl chloride (1.74 ml, 20 mmol) and dimethylformamide (catalytic, 3 drops) and the reaction stirred for 1 h. The solvent was evaporated and the residue co-evaporated with toluene (3×20 ml). The resulting acid chloride was dissolved in 1,2-dichloroethane (40 ml), methyl 2-amino-4-chlorobenzoate (1.5 g, 8 mmol) added and the reaction refluxed for 2 h. The residue remaining on evaporation of the solvent was triturated with diethyl ether to afford methyl 4-chloro-2-(3-thienyl)acetamidobenzoate as a tan solid (1 g), m.p. 96°-97° C. To a solution of the foregoing amide (0.5 g, 1.6 mmol) in tetrahydrofuran (25 ml) was added a solution of potassium hexamethyldisilazide in toluene (0.5M, 4 mmol) and the reaction stirred for 2 h. Methanol (5 ml) was added and the solvent evaporated. The residue was partitioned between aqueous sodium hydroxide (1M, 20 ml) and diethyl ether (20 ml), and the aqueous layer acidified with hydrochloric acid (5M). The resultant precipitate was collected and recrystallised from dimethylformamide/water to afford the title compound as a white solid; m.p. 341°-344° C. (from DMF/H2O) (Found: C, 55.07; H, 2.86; Cl, 12.94; N, 5.16; S, 11.42; C13H8ClNO2S, 0.5 H2O requires C, 55.32; H, 3.03, Cl, 12.56; N, 4.96; S, 11.36%); δ(DMSO-d6) 7.22 (1H, dd, J=8.6 and 2 Hz, 6-H), 7.31 (1H, s, 8-H), 7.43 (1H, d, J=4.9 Hz, 5'-H), 7.49-7.51 (1H, m, 4'-H), 7.76 (1H, s, 2'-H), 7.98 (1H, d, J=8.6 Hz, 5-H), 11.55 (1H, s, NH); m/z 277 (M+).

Workup

  1. customthe solvent evaporated
  2. customThe residue was partitioned between aqueous sodium hydroxide (1M, 20 ml) and diethyl ether (20 ml)
  3. customThe resultant precipitate was collected
  4. customrecrystallised from dimethylformamide/water

Sources & evidence

ORD record
ord-aec359cedf8b4879a3af5f7b90844ffc
Source dataset
uspto-grants-1993_12
Patent number
US05268378

Reaction notes

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