Acetic Acid → HCID 11002518, compound

HRID 1108166Notes

Reaction equation

HRID 1108166 reaction equation
[Cl:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH:20]([F:22])[F:21])(=[O:19])=[O:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)=[O:4].C(O)(=O)C.[BH4-].[Na+].Cl>O.O1CCCC1>[Cl:1][CH2:2][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH:20]([F:22])[F:21])(=[O:18])=[O:19])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)[OH:4]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 10980869HCID 10980869, compound

Product 1

HCID 11002518HCID 11002518, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a 500-mL sidearm flask equipped with a thermometer and nitrogen inlet was charged 47.0 g (0.130 mol) of ca. 95%-pure 2-chloro-1-[4'-[(difluoromethyl) -sulfonyl][1,1'-biphenyl]-4-yl]ethanone, 200 mL of tetrahydrofuran, 1.40 mL (23 mmol) of glacial acetic acid, and 10 mL of water. The orange solution was cooled to 5° C. and 2.4 g (31 mmol) of sodium borohydride was added in three portions over about 15 minutes. The mixture was held for 15 minutes at 10° C., diluted with 200 mL of water, and acidified to pH 2 with about 40 mL of aqueous 1N HCl. Most of the THF was removed in vacuo and the oil was extracted with 400 mL of ethyl acetate. The ethyl acetate layer was washed in succession with water, aqueous NaHCO3, and aqueous NaCl, then dried with MgSO4, filtered, and concentrated to dryness. Then residue was crystallized from 200 mL of 1:1 toluene/hexanes, filtered, and washed with 50 mL of 1:1 toluene/hexanes to afford 35.3 g (78% yield) of product as a pale orange solid, m.p. 104-107° C.; a sample purified by chromatography and crystallization from EtOAc/hexanes had m.p. 111-112° C. 1H-NMR (CDCl3) δ3.3 (br s, 1H), 3.7 (dd, 1H), 3.8 (dd, 1H), 5.0 (dd, 1H), 6.23 (t, 1H, J=60 Hz), 7.55 (d, 2H), 7.65 (d, 2H), 7.82 (d, 2H), 8.05 (d, 2H). 13C-NMR (CDCl3) δ50.5, 73.5, 114.7 (t, JCF =286 Hz), 126.9, 127.7, 128.1, 130.1, 131.1, 138.6, 141.0, 148.1 ppm. 19F-NMR(CDCl3) δ-121.8 ppm (d, JHF =53 Hz). Mass spectrum m/z=346 (M+), 297 (M+ --CH2Cl, base peak), 182 amu.

Workup

  1. customTo a 500-mL sidearm flask equipped with a thermometer and nitrogen inlet
  2. customMost of the THF was removed in vacuo
  3. extractionthe oil was extracted with 400 mL of ethyl acetate
  4. washThe ethyl acetate layer was washed in succession with water, aqueous NaHCO3, and aqueous NaCl
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThen residue was crystallized from 200 mL of 1:1 toluene/hexanes
  9. filtrationfiltered
  10. washwashed with 50 mL of 1:1 toluene/hexanes

Sources & evidence

ORD record
ord-badd6c38722d4ddb9ec19502e86addc7
Source dataset
uspto-grants-2000_05
Patent number
US06063932

Reaction notes

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