Acetic Acid → 3-(4-(1-(2,2-Dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one

HRID 1582359Notes

Reaction equation

HRID 1582359 reaction equation
[CH3:1][C:2]1([CH3:34])[O:6][C@H:5]([C:7]([N:9]2[CH2:14][CH2:13][C:12]([C:15]3[C:20]([F:21])=[CH:19][C:18]([N:22]4[CH2:26][C@H:25]([CH2:27][O:28]C(=O)C)[O:24][C:23]4=[O:32])=[CH:17][C:16]=3[F:33])=[CH:11][CH2:10]2)=[O:8])[CH2:4][O:3]1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C.C(=O)(O)[O-].[Na+]>CO>[CH3:1][C:2]1([CH3:34])[O:6][C@H:5]([C:7]([N:9]2[CH2:14][CH2:13][C:12]([C:15]3[C:16]([F:33])=[CH:17][C:18]([N:22]4[CH2:26][C@H:25]([CH2:27][OH:28])[O:24][C:23]4=[O:32])=[CH:19][C:20]=3[F:21])=[CH:11][CH2:10]2)=[O:8])[CH2:4][O:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 207256423-(4(1-(2,2-Dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-acetoxymethyloxazolidin-2-one

Product 1

HCID 207256433-(4-(1-(2,2-Dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-hydroxymethyloxazolidin-2-oneYield 92.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-(4-(1-(2,2-Dimethyl-1,3-dioxolan-4(S)-ylcarbonyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-acetoxymethyloxazolidin-2-one (8.64 g, 18 mM) was suspended in methanol (350 ml) and stirred at ambient temperature under nitrogen. Potassium carbonate (3.73 g, 27 mM) was added, and the mixture stirred for 20 minutes only, then neutralised immediately by the addition of acetic acid (2 ml). Saturated aqueous sodium bicarbonate (50 ml) was added, the methanol evaporated, and the residue diluted with water (100 ml) before extraction of the organics into dichloromethane (250 ml+100 ml). The extract was washed with brine (100 ml), dried (magnesium sulfate), evaporated and crude product purified by chromatography on a 300 g silica vacuum sinter column, eluting with a gradient from 0% to 20% methanol in dichloromethane. Relevant fractions were combined to give the desired product (7.3 g). NMR (DMSO-d6) δ: 1.29 (s, 3H); 1.32 (s, 3H); 2.29 (br, 1H); 2.38 (br, 1H); 3.48-3.76 (complex m, 4H); 3.82 (dd, 1H); 4.05 (complex m, 4H); 4.21 (dd, 1H); 4.72 (m, 1H); 4.90 (dd, 1H); 5.22 (t, 1H); 5.86 (s, 1H); 7.35 (d, 2H). MS (ESP): 439 (MH+) for C21H24F2N2O6

Workup

  1. stirringthe mixture stirred for 20 minutes only
  2. customthe methanol evaporated
  3. additionthe residue diluted with water (100 ml) before extraction of the organics into dichloromethane (250 ml+100 ml)
  4. washThe extract was washed with brine (100 ml)
  5. dry with materialdried (magnesium sulfate)
  6. customevaporated
  7. customcrude product purified by chromatography on a 300 g silica vacuum sinter column
  8. washeluting with a gradient from 0% to 20% methanol in dichloromethane

Sources & evidence

ORD record
ord-938550fe0c6d479a9ae41a5c9e4400dc
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Reaction notes

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