Pyridine → 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

HRID 1582358Notes

Reaction equation

HRID 1582358 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][C:5]([C:8]2[C:13]([F:14])=[CH:12][C:11]([N:15]3[CH2:19][C@H:18]([CH2:20][O:21][C:22](=[O:24])[CH3:23])[O:17][C:16]3=[O:25])=[CH:10][C:9]=2[F:26])=[CH:4][CH2:3]1.N1C=CC=CC=1.[CH3:33][C:34]1([CH3:42])[O:38][C@H:37]([C:39](Cl)=[O:40])[CH2:36][O:35]1.C(=O)(O)[O-].[Na+]>ClCCl>[CH3:33][C:34]1([CH3:42])[O:38][C@H:37]([C:39]([N:2]2[CH2:7][CH2:6][C:5]([C:8]3[C:13]([F:14])=[CH:12][C:11]([N:15]4[CH2:19][C@H:18]([CH2:20][O:21][C:22](=[O:24])[CH3:23])[O:17][C:16]4=[O:25])=[CH:10][C:9]=3[F:26])=[CH:4][CH2:3]2)=[O:40])[CH2:36][O:35]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 516892Sodium BicarbonateHCID 10374773HCID 10374773, compoundHCID 20725654HCID 20725654, compound

Product 1

HCID 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-oneYield 97.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-(4-(1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-acetoxymethyloxazolidin-2-one hydrochloride (14.5 g, 37.3 mM) was suspended in dry dichloromethane (300 ml) under nitrogen at 0°, and treated with pyridine (9.78 g, 0.12 M). A solution of 2,2-dimethyl-1,3-dioxolan-4(S)-ylcarbonyl chloride (9.59 g, 75.6 mM) in dichloromethane (100 ml) was added dropwise, and stirring continued for 3 hours, allowing the temperature to rise to ambient. Aqueous sodium bicarbonate (5%, 300 ml) was added, and stirring continued for 30 minutes. The organic phase was separated, dried (magnesium sulfate), filtered, and evaporated to dryness after the addition of toluene (20 ml). The solid residue was triturated with a mixture of diethyl ether (250 ml) and isohexane (150 ml), and solid filtered to give the title compound (17.5 g). NMR (DMSO-d6) δ: 1.30 (2×s, 6H); 2.02 (s, 3H); 2.28 (br, 1H); 2.39 (br, 1H); 3.67 (t overlapping m, 2H); 3.83 (dd, 1H); 4.00-4.32 (overlapping m, 7H); 4.90 (overlapping m, 2H); 5.86 (s, 1H); 7.34 (d, 2H). MS (ESP): 481 (MH+) for C23H26F2N2O7

Workup

  1. stirringstirring
  2. waitcontinued for 30 minutes
  3. customThe organic phase was separated
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated to dryness
  7. additionafter the addition of toluene (20 ml)
  8. customThe solid residue was triturated with a mixture of diethyl ether (250 ml) and isohexane (150 ml), and solid
  9. filtrationfiltered

Sources & evidence

ORD record
ord-5ad9f41e6e474c98afcbdca0163d0f05
Source dataset
uspto-grants-2004_05
Patent number
US06734200B1

Reaction notes

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