Sodium hydride → HCID 86704647, compound

HRID 1508600Notes

Reaction equation

HRID 1508600 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[O:13][C:12](=[O:14])[NH:11][C@H:10]2[CH3:15])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[H-].[Na+].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([O:34][CH3:35])=[O:33])=[CH:28][C:27]=2[CH3:36])=[CH:22][C:21]=1[C:37]1[C:38]([CH2:45]OS(C)(=O)=O)=[N:39][C:40]([S:43][CH3:44])=[N:41][CH:42]=1>C1COCC1>[Cl:8][C:6]1[CH:5]=[C:4]([C@H:9]2[O:13][C:12](=[O:14])[N:11]([CH2:45][C:38]3[C:37]([C:21]4[CH:22]=[C:23]([C:26]5[CH:31]=[CH:30][C:29]([C:32]([O:34][CH3:35])=[O:33])=[CH:28][C:27]=5[CH3:36])[CH:24]=[CH:25][C:20]=4[O:19][CH3:18])=[CH:42][N:41]=[C:40]([S:43][CH3:44])[N:39]=3)[C@H:10]2[CH3:15])[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 59287334HCID 59287334, compoundHCID 86704648HCID 86704648, compound

Product 1

HCID 86704647HCID 86704647, compoundYield 61.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To (4S,5R)-5-(3,5-dichlorophenyl)-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE XX—see table 18, 202 mg, 0.821 mmol) in THF (6 mL) at 0° C. was added sodium hydride (60 wt %, 37.3 mg, 0.933 mmol). The reaction was stirred at 0° C. for 1 hour and a solution of methyl 4′-methoxy-2-methyl-3′-[2-(methylsulfanyl)-4-{[(methylsulfonyl)oxy]methyl}pyrimidin-5-yl]biphenyl-4-carboxylate (364 mg, 0.746 mmol) in THF (500 μL) was added. The reaction was allowed to warm to room temperature overnight. The reaction was cooled to 0° C. and was quenched with HCl (1 N, 373 μL) and the reaction was poured into saturated aqueous NaHCO3 and ethyl acetate. The organic was washed with brine, was dried (Na2SO4), filtered, and concentrated. The resultant residue was purified by column chromatography to yield methyl 3′-[4-{[(4S,5R)-5-(3,5-dichlorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]methyl}-2-(methylsulfanyl)pyrimidin-5-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (295 mg, 0.462 mmol). LCMS calc.=638.1. found=638.2.

Workup

  1. temperatureto warm to room temperature overnight
  2. temperatureThe reaction was cooled to 0° C.
  3. customwas quenched with HCl (1 N, 373 μL)
  4. additionthe reaction was poured into saturated aqueous NaHCO3 and ethyl acetate
  5. washThe organic was washed with brine
  6. dry with materialwas dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resultant residue was purified by column chromatography

Sources & evidence

ORD record
ord-6eb9aae5d9984ab7ae9fc3b2d9e89e2e
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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