Hydrochloric Acid → (S)-2-(2,4-difluorophenyl)-1-isobutyryloxy-3-methanesulfonyloxy-2-propanol

HRID 2256476노트

반응식

HRID 2256476 반응식
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]([OH:19])([CH2:12][O:13][C:14](=[O:18])[CH:15]([CH3:17])[CH3:16])[CH2:10][OH:11].[CH3:20][S:21](Cl)(=[O:23])=[O:22].N1C=CC=CC=1.Cl>C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:19])([CH2:10][O:11][S:21]([CH3:20])(=[O:23])=[O:22])[CH2:12][O:13][C:14](=[O:18])[CH:15]([CH3:16])[CH3:17]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 11150004(R)-2-(2,4-difluorophenyl)-3-isobutyryloxy-1,2-propanediol

생성물 1

HCID 11279597(S)-2-(2,4-difluorophenyl)-1-isobutyryloxy-3-methanesulfonyloxy-2-propanol수율 98.6%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

Into a solution wherein 12 g of (R)-2-(2,4-difluorophenyl)-3-isobutyryloxy-1,2-propanediol obtained in Example 40 was dissolved in 120 ml of ethyl acetate was added dropwise 10 g of methanesulfonyl chloride at a temperature of 0° to 5° C., and thereto was added dropwise 6.92 g of pyridine at a temperature of 0° to 5° C. After dropping, the resulting liquid was stirred at room temperature for 16 hours. To the reaction mixture was added 400 ml of 1N hydrochloric acid and an organic layer separated. The organic layer was washed with saturated aqueous solution with sodium hydrogencarbonate and with saturated aqueous solution with sodium chloride, and dried over anhydrous sodium sulfate. The solvent was removed trader reduced pressure and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1) to give 15.2 g of oily (S)-2-(2,4-difluorophenyl)-1-isobutyryloxy-3-methanesulfonyloxy-2-propanol. An optical purity thereof was determined in the same manner as in Example 35. (Elution time: 22.5 minutes ((R)-form) and 24.7 minutes ((S)-form)). 1H-NMR (400 MHz, CDCl3) δ ppm: 7.71-7.68 (1H, m), 6.96-6.92 (1H, m), 6.85-6.81 (1H, m), 4.59-4.47 (4H, m), 3.04 (3H, s), 2.51-2.48 (1H, m), 1.06-1.04 (6H, m) Optical purity: 96.0% ee

후처리

  1. customan organic layer separated
  2. washThe organic layer was washed with saturated aqueous solution with sodium hydrogencarbonate and with saturated aqueous solution with sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed trader reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1)

출처 및 근거

ORD 기록
ord-91cf5411ae1648589a1c96777a8f7630
출처 데이터셋
uspto-grants-1997_08
특허 번호
US05654472

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