Hydrochloric Acid → 1,2-Epoxy-2-(2,5-difluorophenyl)butan-3-ol

HRID 731021Notes

Reaction equation

HRID 731021 reaction equation
Cl[CH2:2][C:3]([C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[F:21])([OH:13])[CH:4]([O:6]C(=O)C(C)(C)C)[CH3:5].C[O-].[Na+].Cl>C1COCC1.CO>[O:13]1[C:3]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=2[F:21])([CH:4]([OH:6])[CH3:5])[CH2:2]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10942334Sodium MethoxideHCID 231170421-Chloro-2-(2,5-difluorophenyl)-3-pivaloyloxybutan-2-ol

Product 1

HCID 230742631,2-Epoxy-2-(2,5-difluorophenyl)butan-3-olYield 79%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1.70 g (5.3 mmol) of 1-chloro-2-(2,5-difluorophenyl)-3-(pivaloyloxy)butan-2-ol ((2S,3R)/(2R,3R)=94/6) in 20 mL of THF was cooled to 0° C., and 3.5 g (17.8 mmol) of a 28% solution of NaOMe in methanol was added thereto. The reaction was performed for 5 hours, and 20 mL of 1 M hydrochloric acid was added to stop the reaction. Then, extraction was performed with ethylacetate (30 mL). After drying over anhydrous sodium sulfate, concentration was performed under reduced pressure to obtain 1.51 g of a crude product. The resulting product was purified by column on silica gel to obtain 0.838 g of the title compound (yield: 79%) ((2R,3R)/(2S,3R)=98/2 (the diastereomeric ratio was measured by HPLC under the same HPLC measurement conditions as those in Example 10, (2R,3R) 32 minutes, (2S,3R) 30 minutes). 1H-NMR (400 MHz, CDCl3) (2R,3R) δ: 1.70 (d, 3H, J=6.6 Hz), 2.80 (d, 1H, J=5.1 Hz), 3.34 (d, 1H, J=5.1 Hz), 4.17 (q, 1H, 6.6 Hz), 6.98-7.00 (m, 2H), 7.14-7.26 (m, 1H)

Workup

  1. customthe reaction
  2. extractionThen, extraction
  3. dry with materialAfter drying over anhydrous sodium sulfate, concentration
  4. customto obtain 1.51 g of a crude product
  5. customThe resulting product was purified by column on silica gel

Sources & evidence

ORD record
ord-c3d04a554bf74fc4b58f8453741186c0
Source dataset
uspto-grants-2009_09
Patent number
US07582781B2

Reaction notes

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