Water → (S)-6-Fluoro-3-[1-(3-hydroxy-2-methylpropyl)-4-piperidinyl]-1,2-benzisothiazole fumarate

HRID 357418

반응식

HRID 357418 반응식
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][S:8][C:4]=2[CH:3]=1.Br[CH2:18][C@H:19]([CH3:22])[CH2:20][OH:21].O.[C:24]([OH:31])(=[O:30])/[CH:25]=[CH:26]/[C:27]([OH:29])=[O:28]>CC(C)=O.S([O-])([O-])(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.CCOC(C)=O>[C:24]([OH:31])(=[O:30])/[CH:25]=[CH:26]/[C:27]([OH:29])=[O:28].[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:18][C@H:19]([CH3:22])[CH2:20][OH:21])[CH2:13][CH2:14]3)=[N:7][S:8][C:4]=2[CH:3]=1

참가 물질

8

반응물 4

HCID 962Water2회HCID 444972Fumaric AcidHCID 10441885(R)-(-)-3-Bromo-2-methyl-1-propanolHCID 185049766-Fluoro-3-(4-piperidinyl)-1,2-benzisothiazole

생성물 1

HCID 22868569(S)-6-Fluoro-3-[1-(3-hydroxy-2-methylpropyl)-4-piperidinyl]-1,2-benzisothiazole fumarate수율 69.1%

시약·촉매·용매 3

HCID 11433187Bis(tetrabutylammonium) sulphate촉매HCID 180Acetone용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisothiazole (4.6 g, 20 mmol), (R)-(-)-3-bromo-2-methyl-1-propanol (3.0 g, 20 mmol), K2 CO3 (2.7 g, 20 mmol), tetrabutylammonium sulfate (0.058 g), CH3 CN (95 ml) and H2O (19 ml) was stirred and refluxed for 4.5 hours. After standing at ambient temperature for 16 hours, the reaction was poured into H2O, and subsequent extractive workup of the aqueous with EtOAc yielded 6.8 g of a partially solidified oil. The product was purified by flash chromatography on silica gel, eluting the column with CH2Cl2, then 2% MeOH--CH2Cl2 and finally 5% MeOH--CH2Cl2. Concentration of the appropriate fractions yielded 5.2 g of a waxy solid. The solid was dissolved in acetone and fumaric acid (1.9 g, 1.0 eq) was added and the reaction briefly heated at reflux. The resultant fumarate salt precipitated from solution yielding 4.8 g of white solid. The compound was recrystallized from acetonitrile to yield 3.1 g (36%) of the alcohol as a white solid, m.p.=151°-153° C.

후처리

  1. temperaturerefluxed for 4.5 hours
  2. customyielded 6.8 g of a partially solidified oil
  3. customThe product was purified by flash chromatography on silica gel
  4. washeluting the column with CH2Cl2
  5. customConcentration of the appropriate fractions yielded 5.2 g of a waxy solid
  6. customthe reaction
  7. temperaturebriefly heated
  8. temperatureat reflux
  9. customThe resultant fumarate salt precipitated from solution

출처 및 근거

ORD 기록
ord-3fc8b1e9080447b2b4041f5cf01c12a3
출처 데이터셋
uspto-grants-1998_11
특허 번호
US05840727

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