Carbon Dioxide → 3-(4-(1-Benzyl-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-acetoxy-methyloxazolidin-2-one

HRID 1582357Notes

Reaction equation

HRID 1582357 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[C:19]([F:20])=[CH:18][C:17]([N:21]3[CH2:25][C@H:24](CO)[O:23][C:22]3=[O:28])=[CH:16][C:15]=2[F:29])=[CH:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30]([O:33]C(=O)C)(=[O:32])[CH3:31].[C:37](=O)(O)[O-].[Na+].C(=O)=O>ClCCl.CN(C)C1C=CN=CC=1.C(N(CC)CC)C>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[C:15]([F:29])=[CH:16][C:17]([N:21]3[CH:25]([CH3:37])[C@H:24]([O:33][C:30](=[O:32])[CH3:31])[O:23][C:22]3=[O:28])=[CH:18][C:19]=2[F:20])=[CH:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 11304129(5R)-3-(4-(1-benzyl-1,2,5,6-tetrahydropyridin-4-yl)-3,5-difluorophenyl)-5-hydroxymethyloxazolidin-2-one

Product 1

HCID 695849183-(4-(1-Benzyl-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-acetoxy-methyloxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

3-(4-(1-Benzyl-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-hydroxymethyloxazolidin-2-one (20 g, 50 mM, see WO 97-30995) was suspended by stirring in dry dichloromethane (400 ml) under nitrogen at 0°, and treated with triethylamine (5.5 g, 54.4 mM) and 4-dimethylaminopyridine (0.3 g, 2.7 mM). Acetic anhydride (5.3 g, 52 mM) was added dropwise to give a solution, which was stirred for 1 hour, allowing the temperature to rise to ambient. The mixture was shaken with 5% aqueous sodium bicarbonate (200 ml) until carbon dioxide evolution ceased. The organic phase was separated, dried (magnesium sulfate) and evaporated, then azeotroped with toluene (2×50 ml) to give semi-crystalline product of sufficient purity for the next stage (24 g). NMR (DMSO-d6) δ: 2.03 (s, 3H); 2.30 (br, 2H); 2.61 (t, 2H); 3.04 (m, 2H); 3.58 (s, 2H); 3.82 (dd, 1H); 4.14 (t, 1H); 4.23 (dd, 1H); 4.30 (dd, 1H); 4.95 (m, 1H); 5.78 (s, 1H); 7.30(s overlapping m, 7H). MS (ESP): 443 (MH+) for C24H24F2N2O4

Workup

  1. customto give a solution, which
  2. customThe organic phase was separated
  3. dry with materialdried (magnesium sulfate)
  4. customevaporated
  5. customazeotroped with toluene (2×50 ml)
  6. customto give semi-crystalline product of sufficient purity for the next stage (24 g)

Sources & evidence

ORD record
ord-22c6f1167f434faea3a24f55ac14c1cf
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Reaction notes

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