Ammonium Chloride → (R)-[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methanol

HRID 2288764Notes

Reaction equation

HRID 2288764 reaction equation
[C:1]([N:11]1[CH2:18][C@@H:17]2[C@@H:13]([CH2:14][N:15]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26](OCC4C=CC=CC=4)=[O:27])=[CH:21][C:20]=3[F:36])[CH2:16]2)[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C([Li])CCC.C([O:47][CH2:48][C@@H:49]1[O:51][CH2:50]1)(=O)CCC.[Cl-].[NH4+]>C1COCC1>[C:1]([N:11]1[CH2:12][C@@H:13]2[C@@H:17]([CH2:16][N:15]([C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:50][C@H:49]([CH2:48][OH:47])[O:51][C:26]4=[O:27])=[CH:21][C:20]=3[F:36])[CH2:14]2)[CH2:18]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 54105388cis-3-(Carbobenzyloxy)-7-[4-[(carbobenzyloxy)amino]-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octaneHCID 178418339Butyllithium

Product 1

HCID 53649140(R)-[3-[4-[cis-3-(carbobenzyloxy)-3,7-diazabicyclo[3.3.0]octan-7-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a flame dried flask cooled to -78° C. and equipped with a nitrogen inlet is introduced cis-3-(carbobenzyloxy)-7-[4-[(carbobenzyloxy)amino]-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane (7.25 g, 14.81 mmol), THF (100 mL), and 1.6 M butyl lithium (9.72 mL, 15.55 mmol). The reaction is stirred at -78° C. for 1 hour before (R)-(-)-glycidyl butyrate (2.26 mL, 15.99 mmol) is added slowly and stirred for 2 hours at -78° C. and 15 hours at ambient temperature. Saturated ammonium chloride (50 mL) is added and the aqueous phase is extracted with ethyl acetate (2×50 mL). The extracts are combined, washed with saline (50 mL), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 100 mL), eluting with chloroform/methanol (99/1). The appropriate fractions are combined (Rf =0.13, TLC, chloroform/methanol, 95/5) and concentrated in vacuo to give the title compound, mp 168-171° C.

Workup

  1. customTo a flame dried flask
  2. customequipped with a nitrogen inlet
  3. additionis added slowly
  4. extractionthe aqueous phase is extracted with ethyl acetate (2×50 mL)
  5. washwashed with saline (50 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customchromatographed on silica gel (230-400 mesh, 100 mL)
  9. washeluting with chloroform/methanol (99/1)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a778f36a547c47f7a57027485f80cd3e
Source dataset
uspto-grants-2000_07
Patent number
US06090820

Reaction notes

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