Sodium Hydroxide → 4-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid

HRID 572607Notes

Reaction equation

HRID 572607 reaction equation
[C:1]([C:3]1[C:4]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[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+]>C1COCC1.CO.O>[C:1]([C:3]1[C:4]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[C:5]([C:14]([OH:16])=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68627563Ethyl 4-cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxylate

Product 1

HCID 441558974-Cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acidYield 86%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of ethyl 4-cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxylate (0.077 g, 0.21 mmol) in THF/MeOH/water (1:1:1) (6 mL) was added sodium hydroxide (0.2 g, 5 mmol). The reaction mixture was allowed to stir at 50° C. for 6 h and was concentrated. The residue was acidified to pH 1-2 with 1N HCl and was extracted with EtOAc. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated to give 4-cyano-3-(4-methoxyphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid (77) (0.061 g, 86%). LCMS: (FA) ES+ 345. 1H NMR (400 MHz, d6-DMSO) δ: 7.27-7.31 (m, 2H), 6.95-6.99 (m, 2H), 3.80 (s, 3H), 3.76-3.78 (m, 4H) and 3.56-3.58 (m, 4H).

Workup

  1. concentrationwas concentrated
  2. extractionwas extracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-07ef624948914221ba73384076a0fe64
Source dataset
uspto-grants-2015_05
Patent number
US09029411B2

Reaction notes

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