Sodium Hydroxide → 5-Carbamoyl-4-cyclobutyl-2-methylbenzoic acid

HRID 1487843Notes

Reaction equation

HRID 1487843 reaction equation
[C:1]([C:3]1[C:4]([CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:6]([CH3:13])=[C:7]([CH:12]=1)[C:8]([O:10]C)=[O:9])#[N:2].[OH-:18].[Na+]>CS(C)=O>[C:1]([C:3]1[C:4]([CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:6]([CH3:13])=[C:7]([CH:12]=1)[C:8]([OH:10])=[O:9])(=[O:18])[NH2:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68288299Methyl 5-cyano-4-cyclobutyl-2-methylbenzoate2×

Product 1

HCID 900214605-Carbamoyl-4-cyclobutyl-2-methylbenzoic acidYield 96%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a 1-L round bottom flask was added methyl 5-cyano-4-cyclobutyl-2-methylbenzoate (compound 6.4, 12.00 g, 52.3 mmol) and dissolved in DMSO (100 mL). With stirring, aqueous sodium hydroxide (1 M, 260 mL, 260 mmol) was added carefully and the mixture was purged with nitrogen. The mixture was stirred at 95° C. for 13 hours and then cooled to room temperature. The solution was washed with diethyl ether (100 mL) and the basic aqueous was acidified to pH˜2 by slow addition of aqueous HCl (1M) followed by aqueous H3PO4 (1M). The precipitated solids were filtered, and washed with water (2×100 mL), then dried to constant mass to yield the title compound as a white powder (11.68 g, 96%). m/z (ES−) 232 (M−H)−. 1H NMR (400 MHz, DMSO-d6): δ 12.75 (br s, 1H), 7.75 (s, 1H), 7.74 (br s, 1H), 7.34 (br s, 1H), 7.28 (s, 1H), 3.90 (app p, J=9.0 Hz, 1H), 2.56 (s, 3H), 2.32-2.20 (m, 2H), 2.16-2.02 (m, 2H), 2.00-1.87 (m, 1H), 1.82-1.71 (m, 1H).

Workup

  1. customthe mixture was purged with nitrogen
  2. stirringThe mixture was stirred at 95° C. for 13 hours
  3. washThe solution was washed with diethyl ether (100 mL)
  4. additionthe basic aqueous was acidified to pH˜2 by slow addition of aqueous HCl (1M)
  5. filtrationThe precipitated solids were filtered
  6. washwashed with water (2×100 mL)
  7. customdried to constant mass

Sources & evidence

ORD record
ord-99e892c35b4c4ec587fa727904675632
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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