Lithium hydroxide, monohydrate → 2-((2-Chloro-4-(dimethylcarbamoyl)phenyl)(methyl) carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acid

HRID 84520Notes

Reaction equation

HRID 84520 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8](=[O:12])[N:9]([CH3:11])[CH3:10])[CH:5]=[CH:4][C:3]=1[N:13]([CH3:34])[C:14]([C:16]1[S:33][C:19]2[C:20]3[CH:28]=[CH:27][C:26]([C:29]([O:31]C)=[O:30])=[CH:25][C:21]=3[O:22][CH2:23][CH2:24][C:18]=2[CH:17]=1)=[O:15].O[Li].O>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8](=[O:12])[N:9]([CH3:10])[CH3:11])[CH:5]=[CH:4][C:3]=1[N:13]([CH3:34])[C:14]([C:16]1[S:33][C:19]2[C:20]3[CH:28]=[CH:27][C:26]([C:29]([OH:31])=[O:30])=[CH:25][C:21]=3[O:22][CH2:23][CH2:24][C:18]=2[CH:17]=1)=[O:15]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 56834268Methyl 2-((2-chloro-4-(dimethylcarbamoyl)phenyl)(methyl)-carbamoyl)-4,5-dihydrobenzo[b] thieno[2,3-d]oxepine-8-carboxylate

Product 1

HCID 568342692-((2-Chloro-4-(dimethylcarbamoyl)phenyl)(methyl) carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acidYield 82.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-((2-chloro-4-(dimethylcarbamoyl)phenyl)(methyl)-carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylate (25.00 g, 50.1 mmol) was dissolved in THF (50 mL) and water (50 mL). The solution was treated with LiOH.H2O (5.26 g, 125.3 mmol). The reaction mixture was stirred at room temperature for 2 h. Concentrated to remove the solvent THF and the mixture was acidified by 2N HCl. The resulting precipitate was filtrated, washed by water, dried to give 2-((2-chloro-4-(dimethylcarbamoyl)phenyl)(methyl) carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylic acid (20.00 g, 82%). ESI-MS: 485.1. 1H NMR (CDCl3, 400 MHz): δ7.66-7.60 (m, 3H, ArH), 7.46-7.42 (m, 3H, ArH), 6.99 (s, 1H, ═CH), 4.23 (t, J=5.0 Hz, 2H, CH2), 3.39 (s, 3H, CH3), 3.14 (s, 3H, CH3), 3.07 (t, J=5.0 Hz, 2H, CH2), 3.02 (s, 3H, CH3).

Workup

  1. concentrationConcentrated
  2. customto remove the solvent THF
  3. filtrationThe resulting precipitate was filtrated
  4. washwashed by water
  5. customdried

Sources & evidence

ORD record
ord-bca42b2206dd414788110300e9bc0f9d
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Reaction notes

Loading…