Hydrochloric Acid → (5R)-3-{4-[5-(Dimethoxymethyl)-1-methyl-1H-pyrazol-3-yl]phenyl}-5-(hydroxymethyl)-1,3-oxazolidin-2-one

HRID 456794Notes

Reaction equation

HRID 456794 reaction equation
[CH2:1]([O:3][CH:4]([O:28][CH2:29]C)[C:5]1[N:9]([CH3:10])[N:8]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:27])[O:19][CH2:20][C:21]3C=CC=CC=3)=[CH:13][CH:12]=2)[CH:6]=1)C.[Li]CCCC.[C:36](OC[C@H]1CO1)(=[O:40])CCC.Cl.C(OC)(OC)OC>C1COCC1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(N(CC)CC)C.CO>[CH3:1][O:3][CH:4]([O:28][CH3:29])[C:5]1[N:9]([CH3:10])[N:8]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:21][C@H:20]([CH2:36][OH:40])[O:19][C:18]3=[O:27])=[CH:13][CH:12]=2)[CH:6]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 9005Trimethyl orthoformateHCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 18438601Benzyl 4-[5-(diethoxymethyl)-1-methyl-1H-pyrazol-3-yl]phenylcarbamate2×HCID 178418339Butyllithium

Product 1

HCID 58625204(5R)-3-{4-[5-(Dimethoxymethyl)-1-methyl-1H-pyrazol-3-yl]phenyl}-5-(hydroxymethyl)-1,3-oxazolidin-2-oneYield 49.5%

Reagents, catalysts & solvents 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-CatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

Benzyl 4-[5-(diethoxymethyl)-1-methyl-1H-pyrazol-3-yl]phenylcarbamate (Intermediate 11, 8.29 g, 20.2 mmol), was dissolved in THF (150 ml) and cooled to −70° C. nBuLi (15 ml of a 1.6 M solution in hexanes, 24 mmol) was added dropwise over 10 min. After 25 min at −70° C., (2R)-oxiran-2-ylmethyl butyrate (3.7 ml, 26.2 mmol) was added and the solution was allowed to warm slowly to room temperature over 16 hours. The mixture was poured into 0.25M HCl and extracted with ethyl acetate, the organic layer was washed with saturated NaCl, dried over sodium sulfate and evaporated to give the crude product which was partially hydrolysed to the aldehyde. The crude product was dissolved in 1:1 THF:methanol (12 ml), trimethyl orthoformate (2.6 ml, 24 mmol) and camphorsulfonic acid (100 mg, 0.4 mmol) were added and the solution was warmed at 50° C. for 1 hour. Triethylamine (0.5 ml) was added and the solution was evaporated and purified by chromatography on silica gel, eluting with 60–100% ethyl acetate/hexane, to give the title compound as a white solid (3.47 g).

Workup

  1. additionwas added dropwise over 10 min
  2. extractionextracted with ethyl acetate
  3. washthe organic layer was washed with saturated NaCl
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customto give the crude product which
  7. temperaturethe solution was warmed at 50° C. for 1 hour
  8. customthe solution was evaporated
  9. custompurified by chromatography on silica gel
  10. washeluting with 60–100% ethyl acetate/hexane

Sources & evidence

ORD record
ord-a2da76024d3a46f38ea9689dda5da567
Source dataset
uspto-grants-2007_03
Patent number
US07186738B2

Reaction notes

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