Sodium hydride → HCID 86730137, compound

HRID 1850108Notes

Reaction equation

HRID 1850108 reaction equation
[F:1][C:2]1[N:7]=[C:6](F)[CH:5]=[CH:4][N:3]=1.[CH:9]([C@H:12]1[CH2:16][O:15][C:14](=[O:17])[NH:13]1)([CH3:11])[CH3:10].[H-].[Na+]>CN(C=O)C.O>[F:1][C:2]1[N:7]=[C:6]([N:13]2[C@@H:12]([CH:9]([CH3:11])[CH3:10])[CH2:16][O:15][C:14]2=[O:17])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 1377162,4-DifluoropyrimidineHCID 7157133(4S)-4-(propan-2-yl)-1,3-oxazolidin-2-one

Product 1

HCID 86730137HCID 86730137, compoundYield 33.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2,4-difluoropyrimidine (3.5 mL, 41 mmol) and (S)-4-isopropyloxazolidin-2-one (5.3 g 41 mmol) in 30 mL DMF was cooled to 0° C. under N2 atmosphere. NaH (2.1 g of 60% suspension, 53 mmol) was slowly added. Bubbling exotherm observed. Internal temp was kept below 5° C. After 5 minutes, cold bath was removed. Reaction mixture (a sandy suspension) was allowed to warm to room temp and stir 18 h. The reaction mixture was diluted with water (100 mL) and extracted with (3×75 mL) EtOAc. Organic layer was washed with 50 mL each water, and brine. Dried over Na2SO4, and concentrated on silica gel in vacuo. Column chromatography (EtOAc/heptane 10 to 100% gradient) gave 3.1 g (S)-3-(2-fluoropyrimidin-4-yl)-4-isopropyloxazolidin-2-one (IV) as a crystalline white solid (33%). 1H NMR (400 MHz, CDCl3) δ 8.50 (dd, J=5.8, 2.2 Hz, 1H), 8.19 (dd, J=5.8, 3.8 Hz, 1H), 4.79 (dt, J=8.1, 3.5 Hz, 1H), 4.48-4.34 (m, 2H), 2.64 (heptd, J=7.0, 3.6 Hz, 1H), 1.01 (d, J=7.0 Hz, 3H), 0.90 (d, J=6.9 Hz, 3H). MS m/z 471.8 and 471.8 (M+H)+.

Workup

  1. customBubbling exotherm
  2. customwas kept below 5° C
  3. customcold bath was removed
  4. customReaction mixture (a sandy suspension)
  5. extractionextracted with (3×75 mL) EtOAc
  6. washOrganic layer was washed with 50 mL each water, and brine
  7. dry with materialDried over Na2SO4
  8. concentrationconcentrated on silica gel in vacuo

Sources & evidence

ORD record
ord-695de0d84b834df996520af7df416920
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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