Water → HCID 86723804, compound

HRID 577578Notes

Reaction equation

[CH3:1][C:2]1[C:7]2[C:8](=[O:13])[NH:9][CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[CH:4][C:3]=1[C:14]([O:16]C)=[O:15].[H-].[Na+].[CH2:20]([O:27][C:28]1[C:33]([CH2:34]Cl)=[C:32]([CH3:36])[CH:31]=[C:30]([CH3:37])[N:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.O>CN(C=O)C>[CH2:20]([O:27][C:28]1[C:33]([CH2:34][N:9]2[C:8](=[O:13])[C:7]3[C:2]([CH3:1])=[C:3]([C:14]([OH:16])=[O:15])[CH:4]=[CH:5][C:6]=3[O:12][CH2:11][CH2:10]2)=[C:32]([CH3:36])[CH:31]=[C:30]([CH3:37])[N:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 6-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepine-7-carboxylate (130e, 0.10 g, 0.45 mmol) in DMF (8 mL) was added NaH (54 mg, 1.36 mmol, 60% in oil) at 0° C. After stirring at 0° C. for 10 minutes, 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 0.20 g, 0.77 mmol) was added. The mixture was stirred at room temperature overnight. To the reaction mixture was added H2O (30 mL). The mixture was extracted with EtOAc (2×20 mL). The aqueous layer was acidified with conc. HCl to pH 3 and extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine (4×30 mL), dried over Na2SO4, and concentrated under vacuum to give 4-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-6-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepine-7-carboxylic acid (130f, 0.17 g, 84.7%) as an off-white solid.

Workup

stirringThe mixture was stirred at room temperature overnight
extractionThe mixture was extracted with EtOAc (2×20 mL)
extractionextracted with EtOAc (2×20 mL)
washThe combined organic layers were washed with brine (4×30 mL)
dry with materialdried over Na2SO4
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-40cb8c537bc14a4cbe5a01adc637f0dc
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040515B2

Reaction notes

Loading…