Water → 3-(4-(1-(2,2-Dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)(N-(t-butoxycarbonyl)-3-methylisoxazol-5-ylaminomethyl)oxazolidin-2-one

HRID 8178Notes

Reaction equation

HRID 8178 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]1[O:15][N:14]=[C:13]([CH3:16])[CH:12]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:17][C:18]1([CH3:51])[O:22][C@H:21]([C:23]([N:25]2[CH2:30][CH2:29][C:28]([C:31]3[C:36]([F:37])=[CH:35][C:34]([N:38]4[CH2:42][C@H:41]([CH2:43]OS(C)(=O)=O)[O:40][C:39]4=[O:49])=[CH:33][C:32]=3[F:50])=[CH:27][CH2:26]2)=[O:24])[CH2:20][O:19]1.O>CN(C)C=O>[CH3:51][C:18]1([CH3:17])[O:22][C@H:21]([C:23]([N:25]2[CH2:30][CH2:29][C:28]([C:31]3[C:36]([F:37])=[CH:35][C:34]([N:38]4[CH2:42][C@H:41]([CH2:43][N:10]([C:11]5[O:15][N:14]=[C:13]([CH3:16])[CH:12]=5)[C:8]([O:7][C:3]([CH3:6])([CH3:5])[CH3:4])=[O:9])[O:40][C:39]4=[O:49])=[CH:33][C:32]=3[F:50])=[CH:27][CH2:26]2)=[O:24])[CH2:20][O:19]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 11138073tert-Butyl (3-methylisoxazol-5-yl)carbamateHCID 207256443-(4(1-(2,2-dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-methanesulfonyloxymethyloxazolidin-2-one

Product 1

HCID 571741763-(4-(1-(2,2-Dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)(N-(t-butoxycarbonyl)-3-methylisoxazol-5-ylaminomethyl)oxazolidin-2-oneYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Sodium hydride (60% in oil, 72 mg, 1.8 mM) was suspended in dry N,N-dimethylformamide (3 ml), cooled to 0° under nitrogen, and a solution of 5-(t-butoxycarbonylamino)-3-methylisoxazole (356 mg, 1.8 mM) in N,N-dimethylformamide (3 ml) added. After stirring for 10 minutes, a solution of 3-(4(1-(2,2-dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-methanesulfonyloxymethyloxazolidin-2-one (516 mg, 1.5 mM) in N,N-dimethylformamide (3 ml) was added, and the mixture heated to 40° for 5 hours. After cooling, the mixture was poured into water (50 ml), extracted with dichloromethane (4×20 ml). The organic phase was dried (magnesium sulfate), evaporated and crude product purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient from 50% to 75% ethyl acetate in isohexane. Relevant fractions were combined to give the desired product (420 mg).

Workup

  1. temperaturecooled to 0° under nitrogen
  2. temperaturethe mixture heated to 40° for 5 hours
  3. temperatureAfter cooling
  4. extractionextracted with dichloromethane (4×20 ml)
  5. dry with materialThe organic phase was dried (magnesium sulfate)
  6. customevaporated
  7. customcrude product purified by chromatography on a 10 g silica Mega Bond Elut® column
  8. washeluting with a gradient from 50% to 75% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-69112d76987b4639bb687f96e5828388
Source dataset
uspto-grants-2006_08
Patent number
US07087629B2

Reaction notes

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