Sodium Bicarbonate → 2-Propanol, 2-methyl-, lithium salt (1:1)

HRID 1166016Notes

Reaction equation

HRID 1166016 reaction equation
C([Li:5])CCC.[CH2:6](O[C:14]([NH:16][C:17]1[CH:18]=[CH:19][C:20]([N:24]2[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][F:32])[C:26](=[O:33])[CH2:25]2)=[C:21]([F:23])[CH:22]=1)=O)[C:7]1[CH:12]=CC=C[CH:8]=1.[CH2:34]([O:38][C:39](=[O:43])CCC)[C@@H:35]1[O:37]C1.C(=O)(O)[O-].[Na+]>C1COCC1.O.CO.C(O)(C)(C)C>[CH3:6][C:7]([CH3:12])([O-:37])[CH3:8].[Li+:5].[F:23][C:21]1[CH:22]=[C:17]([N:16]2[CH2:14][C@H:34]([CH2:35][OH:37])[O:38][C:39]2=[O:43])[CH:18]=[CH:19][C:20]=1[N:24]1[CH2:29][CH2:28][N:27]([CH2:30][CH2:31][F:32])[C:26](=[O:33])[CH2:25]1

Participants

10

Reactant 4

HCID 516892Sodium BicarbonateHCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 22716470HCID 22716470, compoundHCID 178418339Butyllithium

Product 2

HCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 54327468HCID 54327468, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of lithium t-butoxide is prepared by addition of n-butyllithium (1.6 M in hexane, 2.9 ml) to a stirred solution of t-butanol (0.43 g) in anhydrous THF (10 ml) at −10° under argon. After cooling to −70°, a solution of 5-benzyloxycarbonylamino-2-(4-[2 fluoroethyl]-3-oxopiperazin-1-yl)fluorobenzene (1.5 g) in dry THF (15 ml) is added. After 10 minutes, (R)-glycidylbutyrate (0.67 g) in dry THF (15 ml) is added to the resulting mixture, and stirring continued at −70° for 15 minutes, before allowing the temperature to rise to 20-25° over 16 hours. Methanol (10 ml) is added, followed by saturated sodium bicarbonate solution (20 ml) and water (10 ml). The organic phase is separated and extracted into ethyl acetate (3×25 ml), washed with saline and dried over magnesium sulfate. The solvent is removed and the residue purified by chromatography (silica; eluting with a gradient increasing in polarity from 0 to 3% methanol in dichloromethane) to give (5R)-3-(3-fluoro-4-[4-(2-fluoroethyl)-3-oxopiperazin-1-yl]phenyl)-5 hydroxymethyloxazolidin-2-one.

Workup

  1. temperatureAfter cooling to −70°
  2. waitcontinued at −70° for 15 minutes
  3. waitto rise to 20-25° over 16 hours
  4. customThe organic phase is separated
  5. extractionextracted into ethyl acetate (3×25 ml)
  6. washwashed with saline
  7. dry with materialdried over magnesium sulfate
  8. customThe solvent is removed
  9. customthe residue purified by chromatography (silica
  10. washeluting with
  11. temperaturea gradient increasing in polarity from 0 to 3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-714f6de46dbb4bbaaa83e5d001cdc20b
Source dataset
uspto-grants-2003_09
Patent number
US06613349B2

Reaction notes

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