Water → (3R,3aS,6S,6aS)-6-Bromohexahydrofuro[3,2-b]furan-3-yl 4-methylbenzenesulfonate

HRID 1887377Notes

Reaction equation

HRID 1887377 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][C@@H:12]2[CH2:16][O:15][C@@H:14]3[C@H:17](OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:18][O:19][C@H:13]23)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Br-:31].[Li+].O>CN(C)C=O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][C@@H:12]2[CH2:16][O:15][C@@H:14]3[C@@H:17]([Br:31])[CH2:18][O:19][C@H:13]23)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 82050Lithium BromideHCID 51033200(3R,3aS,6R,6aS)-6-[(4-methylbenzenesulfonyl)oxy]-hexahydrofuro[3,2-b]furan-3-yl 4-methylbenzene-1-sulfonate

Product 1

HCID 59343394(3R,3aS,6S,6aS)-6-Bromohexahydrofuro[3,2-b]furan-3-yl 4-methylbenzenesulfonateYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A stirred mixture of ditosylate (39) (16.9 g, 37.22 mmol) and lithium bromide (4.85 g, 55.84 mmol) in N,N-dimethylformamide (100 mL) was heated at 100° C. for 27 hours. The mixture was allowed to cool then water (150 mL) added before extracting with tert-butyl methyl ether (1×100 mL then 5 x′50 mL). The organic phase was dried (MgSO4), filtered and reduced in vacuo to give a colourless oil which solidified on standing. Flash chromatography over silica, eluting with ethyl acetate:heptane mixtures 0:100 to 80:20 gave bromotosylate (46) as a white solid (2.86 g, 29%). TLC (Rf=0.45 diethyl ether:heptane, 1:1), analytical HPLC: Rf=16.768 min; HPLC-MS: 363.1/365.0 [M+H]+, 380.1/382.1, 749.0/751.0 [2M+Na]+; [α]D18+64.7° (c=8.5, CHCl3); δH (500 MHz, CDCl3) 2.45 (3H, s, CH3), 3.74 (1H, dd, J=9.60 and 7.05 Hz, CH2), 3.95 (1H, dd, J=9.60 and 6.47 Hz, CH2), 4.14-4.22 (2H, m, CH2), 4.29 (1H, d, J=3.03 Hz, CHBr), 4.68 (1H, d, J=4.03 Hz, CHCH), 4.76 (1H, t, J=4.48 Hz, CHOTs), 4.87 (1H, m, CHCH), 7.36 (2H, brd, J=7.97 Hz, aromatic CH3CCH), 7.83 (2H, brd, J=8.33 Hz, aromatic OSO2CCH). δC (125 MHz, CDCl3) 21.69 (CH3), 50.06 (CHBr), 70.26 (CH2CHOTs), 76.54 (CH2CHBr), 78.27 (CHOTs), 80.17 and 88.80 (CHCHCHOTs), 127.98 and 129.94 (aromatic CH), 133.01 (CHOSO2C quaternary), 145.28 (CH3C quaternary).

Workup

  1. temperatureto cool
  2. extractionbefore extracting with tert-butyl methyl ether (1×100 mL
  3. dry with materialThe organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. customto give a colourless oil which
  6. washFlash chromatography over silica, eluting with ethyl acetate

Sources & evidence

ORD record
ord-4d1bb0dfd2a9475c93ef5d493becabbb
Source dataset
uspto-grants-2013_08
Patent number
US08501744B2

Reaction notes

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