Sodium Hydroxide → 4-Cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylic acid

HRID 2402141Notes

Reaction equation

HRID 2402141 reaction equation
[C:1]([C:3]1[C:4]([CH:19]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=2)[CH2:20][CH:21]=[CH2:22])=[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+]>O1CCCC1.O.CO>[C:1]([C:3]1[C:4]([CH:19]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=2)[CH2:20][CH:21]=[CH2:22])=[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 2

HCID 14798Sodium HydroxideHCID 68006701Ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylate

Product 1

HCID 568328124-Cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylic acidYield 31.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylate (0.211 g, 0.453 mmol) in tetrahydrofuran (8.00 mL) was added 1.000 M of sodium hydroxide in water (10.0 mL) and methanol (4.00 mL). The resulting mixture was stirred at room temp over 3 hrs. The volatiles were removed under reduced pressure, and the resulting mixture was acidified with conc. HCl soln to pH˜2, and extracted with EtOAc (×3). The combined org layer was dried and concentrated to provide a purple syrup. Purification of the crude mixture on HPLC (AA, reverse phase) provided 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylic acid as a white solid (63 mg, 31.8% yield). LCMS: (AA) ES− 391, 393, 395; 1H NMR (400 MHz, MeOD) δ 7.54-7.46 (d, J=1.6 Hz, 1H), 7.45-7.35 (d, J=8.4 Hz, 1H), 7.34-7.24 (dd, J=8.4, 1.6 Hz, 1H), 5.88-5.68 (m, 2H), 5.16-5.05 (dd, J=17.1, 1.7 Hz, 1H), 5.00-4.92 (m, 1H), 3.82-3.71 (t, J=4.8 Hz, 4H), 3.51-3.40 (t, J=4.8 Hz, 4H), 3.05-2.95 (m, 2H).

Workup

  1. customThe volatiles were removed under reduced pressure
  2. extractionextracted with EtOAc (×3)
  3. customThe combined org layer was dried
  4. concentrationconcentrated
  5. customto provide a purple syrup
  6. customPurification of the crude mixture on HPLC (AA, reverse phase)

Sources & evidence

ORD record
ord-e2081622060d411b98f1a55991707d9f
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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