Hydrochloric Acid → HCID 58026144, compound

HRID 2387317Notes

Reaction equation

HRID 2387317 reaction equation
[CH3:1][C:2]([C:12]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:13]=1[CH2:14][O:15]C(=O)C)([CH3:11])[CH2:3][C@:4]1([C:7]([F:10])([F:9])[F:8])[CH2:6][O:5]1.[Li].[OH-].[Na+].Cl.[CH2:28]1COC[CH2:29]1>CS(C)=O>[F:23][C:20]1[CH:21]=[CH:22][C:12]([C:2]([CH3:11])([CH3:1])[CH2:3][C@@:4]([C:7]([F:10])([F:8])[F:9])([OH:5])[CH2:6][C:28]#[CH:29])=[C:13]([CH2:14][OH:15])[CH:19]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 3028194LithiumHCID 58026179HCID 58026179, compound

Product 1

HCID 58026144HCID 58026144, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To 19.1 g (0.057 mol) of acetic acid 2-[1,1-dimethyl-2-((R)-2-trifluoromethyloxiranyl)ethyl]-5-fluorobenzyl ester in 450 mL of DMSO at 15° C. was added 481 mL (0.240 mol) lithium trimethylsilylacetylide (0.5 M in THF). The mixture was warmed to room temperature and stirred for 3 hours. The mixture was then cooled to 0° C. and 300 mL of 3N NaOH was added and the mixture was stirred for 1 hour. The mixture was neutralized by the addition of 400 mL of 3N HCl. The organic phase was removed and the aqueous layers were extracted four times with diethyl ether. The organic phases were washed with 300 mL of water and 300 mL of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude mixture was chromatographed on silica gel using 10-12% ethyl acetate/hexanes to afford 15 g (83%) of (S)-6-(4-fluoro-2-hydroxymethylphenyl)-6-methyl-4-trifluoromethylhept-1-yn-4-ol.

Workup

  1. temperatureThe mixture was then cooled to 0° C.
  2. stirringthe mixture was stirred for 1 hour
  3. customThe organic phase was removed
  4. extractionthe aqueous layers were extracted four times with diethyl ether
  5. washThe organic phases were washed with 300 mL of water and 300 mL of brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude mixture was chromatographed on silica gel using 10-12% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-dee48a2094dc407db4e016a04e8dbcdb
Source dataset
uspto-grants-2012_09
Patent number
US08268859B2

Reaction notes

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