Sodium hydride → HCID 66976191, compound

HRID 1022632Notes

Reaction equation

HRID 1022632 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1.[Br-].[Li+].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C@@H:19]2[O:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][C@H:20]2[CH2:33]OS(C)(=O)=O)=[CH:15][C:14]=1[F:39]>COCCOC.CN(C=O)C.O>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C@@H:19]2[O:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[CH2:21][C@H:20]2[CH2:33][N:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]2=[O:3])=[CH:15][C:14]=1[F:39]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 86663855tert-butyl (6S,7R)-7-(4-chloro-3-fluorophenyl)-6-{[(methylsulfonyl)oxy]methyl}-1,4-oxazepane-4-carboxylateHCID 178516071HCID 178516071, compound

Product 1

HCID 66976191HCID 66976191, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

60% Sodium hydride (45.3 mg, 1.13 mmol) was added to a mixed solution of 2-hydroxypyridine (86 mg, 0.91 mmol) in 1,2-dimethoxyethane (2 ml) and DMF (1 mL) at room temperature. After stirring at room temperature for 5 min, lithium bromide (131 mg, 1.51 mmol) was added at room temperature. After stirring for 10 min, to the reaction mixture was added a solution of tert-butyl (6S,7R)-7-(4-chloro-3-fluorophenyl)-6-{[(methylsulfonyl)oxy]methyl}-1,4-oxazepane-4-carboxylate (331 mg, 0.76 mmol) in 1,2-dimethoxyethane (2 mL). The reaction mixture was stirred at 80° C. overnight. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (267 mg, 0.611 mmol, 81%).

Workup

  1. stirringAfter stirring for 10 min, to the reaction mixture
  2. stirringThe reaction mixture was stirred at 80° C. overnight
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0180fd37d59f4a38aa8a0244fed8b23b
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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