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

HRID 572619Notes

Reaction equation

HRID 572619 reaction equation
[C:1]([C:3]1[C:4]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)=[C:5]([C:14]([O:16]C)=[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:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=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 68629612HCID 68629612, compound

Product 1

HCID 441566374-Cyano-3-(4-methylphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acidYield 93%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4 methyl 4-cyano-3-(4-methylphenyl)-5-morpholin-4-ylthiophene-2-carboxylate (0.060 g, 0.18 mmol) in THF/MeOH/water (2/1/1) (3 mL) was added sodium hydroxide (0.072 g, 1.8 mmol). The reaction mixture was allowed to stir at 50° C. for 3 h and was concentrated. The residue was acidified with 2N HCl and extracted with EtOAc. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The crude product was triturated with diethyl ether and hexanes to give 4-cyano-3-(4-methylphenyl)-5-morpholin-4-ylthiophene-2-carboxylic acid (4) (0.055 g, 93%). LCMS: (FA) ES+ 329.0. 1H NMR (400 MHz, d6-DMSO) δ: 7.20-7.23 (m, 4H), 3.76-3.79 (m, 4H), 3.56-3.59 (m, 4H) and 2.35 (s, 3H).

Workup

  1. concentrationwas concentrated
  2. extractionextracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was triturated with diethyl ether and hexanes

Sources & evidence

ORD record
ord-e4068fd426e440668cdfef4b68f1c0b7
Source dataset
uspto-grants-2015_05
Patent number
US09029411B2

Reaction notes

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