Hydrochloric Acid → 4-Cyano-3-[1-(3,4-dichlorophenyl)-3-(dimethylamino)propyl]-5-(morpholin-4-yl)thiophene-2-carboxylic acid

HRID 2402157Notes

Reaction equation

HRID 2402157 reaction equation
[C:1]([C:3]1[C:4]([CH:19]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=2)[CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])=[C:5]([C:14]([O:16]CC)=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].[OH-].[Na+].Cl>CO.O>[C:1]([C:3]1[C:4]([CH:19]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=2)[CH2:20][CH2:21][N:22]([CH3:24])[CH3:23])=[C:5]([C:14]([OH:16])=[O:15])[S:6][C:7]=1[N:8]1[CH2:9][CH2:10][O:11][CH2:12][CH2:13]1)#[N:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66747499Ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)-3-(dimethylamino)propyl]-5-(morpholin-4-yl)thiophene-2-carboxylate

Product 1

HCID 667477774-Cyano-3-[1-(3,4-dichlorophenyl)-3-(dimethylamino)propyl]-5-(morpholin-4-yl)thiophene-2-carboxylic acidYield 95%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent3×

Procedure

To a solution of ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)-3-(dimethylamino)propyl]-5-(morpholin-4-yl)thiophene-2-carboxylate (29.0 mg, 0.0584 mmol) in methanol (0.500 mL) was added 1.030 M of sodium hydroxide in water (284 uL, 0.284 mmol). The reaction was stirred at rt over 2 days. The mixture was neutralized with 1.00 M of hydrochloric acid in water (0.292 mL), diluted with 5 mL of water and extracted with 10% MeOH/CHCl3 (×5). The combined organic layer was dried and concentrated, and the resulting white syrup/solid was lyophilized to provide 4-cyano-3-[1-(3,4-dichlorophenyl)-3-(dimethylamino)propyl]-5-(morpholin-4-yl)thiophene-2-carboxylic acid as a white solid (26 mg, 95% yield). LCMS: (AA) ES+ 468, 470, 472; 1H NMR (400 MHz, DMSO) δ 7.63-7.52 (d, J=8.4 Hz, 1H), 7.44-7.37 (s, 1H), 7.15-7.02 (d, J=8.1 Hz, 1H), 5.49-5.34 (d, J=9.4 Hz, 1H), 3.73-3.63 (t, J=4.8 Hz, 4H), 3.38-3.31 (dd, J=6.2, 4.0 Hz, 4H), 3.13-2.97 (s, 1H), 2.85-2.73 (s, 1H), 2.72-2.60 (s, 6H), 2.56-2.52 (m, 1H).

Workup

  1. extractionextracted with 10% MeOH/CHCl3 (×5)
  2. customThe combined organic layer was dried
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-4bfb91ba7cfc431392e2497b457a919c
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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