4-Toluenesulfonyl chloride → (3R,3aS,6R,6aR)-6-Hydroxyhexahydrofuro[3,2-b]furan-3-yl 4-methylbenzenesulfonate

HRID 1665864노트

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HRID 1665864 반응식
[CH2:1]1[O:5][C@@H:4]2[C@H:6]([OH:9])[CH2:7][O:8][C@@H:3]2[C@@H:2]1[OH:10].[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1.[OH-].[K+]>C(Cl)(Cl)(Cl)Cl.ClCCl.O>[CH3:21][C:11]1[CH:16]=[CH:15][C:14]([S:17]([O:10][C@@H:2]2[CH2:1][O:5][C@@H:4]3[C@H:6]([OH:9])[CH2:7][O:8][C@H:3]23)(=[O:19])=[O:18])=[CH:13][CH:12]=1

참가 물질

7

반응물 3

HCID 73974-Toluenesulfonyl chlorideHCID 14797Potassium HydroxideHCID 109756241,4:3,6-Dianhydro-D-mannitol

생성물 1

HCID 13014014(3R,3aS,6R,6aR)-6-Hydroxyhexahydrofuro[3,2-b]furan-3-yl 4-methylbenzenesulfonate

시약·촉매·용매 3

HCID 962Water용매2회HCID 5943Carbon Tetrachloride용매HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

Isomannide (40) (10 g, 68.49 mmol) and p-toluenesulphonyl chloride (6.53 g, 34.25 mmol) were dissolved in a mixture of carbon tetrachloride (50 mL), dichloromethane (5 mL) and water (40 mL). The flask was cooled to 0° C. and a solution of potassium hydroxide (1.92 g, 34.25 mmol) in water (5 mL) added dropwise over 30 minutes with stirring. The resulting biphasic mixture was stirred at 0° C. for 7 hours. Then off-white precipitate was collected by filtration in vacuo then partitioned between dichloromethane (30 mL) and water (10 mL). The organic phase was washed with brine (2×10 mL) then dried (Na2SO4), filtered and reduced in vacuo to leave a colourless solid. Recrystallisation from carbon tetrachloride gave monotosylate (50) as colourless granules (3.92 g, 38%). TLC (Rf=0.11, EtOAc:heptane 1:1); analytical HPLC main peak, Rf=10.692 min; HPLC-MS 318.2, 323.1 [M+Na]+, 623.2 [2M+Na]+; [α]D18+72.2° (c=5.4, CHCl3); δH (500 MHz, CDCl3) 2.44 (3H, s, CH3), 3.54 (1H, dd, J=9.31 and 7.23 Hz, OCH2CHOH), 3.78 (1H, dd, J=9.18 and 7.59 Hz, OCH2CHOTs), 3.95 (1H, dd, J=9.36 and 6.45 Hz, OCH2CHOH), 4.01 (1H, dd, J=9.33 and 6.64 Hz, OCH2CHOTs), 4.26 (1H, m, CHOH), 4.42 and 4.48 (each 1H, brt, J=5.03 and 5.00 Hz respectively, CHCHCHOH and CHCHCHOTs), 4.90 (1H, dd, J=12.15 and 6.84 Hz, CHOTs), 7.37 (2H, d, J=8.13 Hz, aromatic CH3CCH), 7.82 (2H, d, J=8.20 Hz, aromatic OSO2CCH); δC (125 MHz, CDCl3) 21.69 (CH3), 70.03 (CH2CHOTs), 72.29 (CHOTs), 74.02 (CH2CHOH), 80.00 (CH2CHOH), 81.36 (CHCHOTs), 81.76 (CHCHOH), 128.00 and 129.89 (aromatic CH), 133.04 (CHOSO2C quaternary), 145.26 (CH3C quaternary).

후처리

  1. stirringThe resulting biphasic mixture was stirred at 0° C. for 7 hours
  2. filtrationThen off-white precipitate was collected by filtration in vacuo
  3. customthen partitioned between dichloromethane (30 mL) and water (10 mL)
  4. washThe organic phase was washed with brine (2×10 mL)
  5. dry with materialthen dried (Na2SO4)
  6. filtrationfiltered
  7. customto leave a colourless solid
  8. customRecrystallisation from carbon tetrachloride

출처 및 근거

ORD 기록
ord-2697b15293eb436dbc256a01f1ec92dd
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08039641B2

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