4-Toluenesulfonyl chloride → ((1S,3'R,4'S,5'S,6'R)-5-chloro-6-(4-ethylbenzyl)-3',4',5'-trihydroxy-3',4',5',6'-tetrahydro-3H-spiro[isobenzofuran-1,2'-pyran]-6'-yl)methyl 4-methylbenzenesulfonate

HRID 1716959Notes

Reaction equation

HRID 1716959 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:18](=[CH:19][C:20]=1[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][CH3:29])=[CH:24][CH:23]=1)[C@:7]1([C@H:12]([OH:13])[C@@H:11]([OH:14])[C@H:10]([OH:15])[C@@H:9]([CH2:16][OH:17])[O:8]1)[O:6][CH2:5]2.[C:30]1([CH3:40])[CH:35]=[CH:34][C:33]([S:36](Cl)(=[O:38])=[O:37])=[CH:32][CH:31]=1>N1C(C)=CC=CC=1C>[CH3:40][C:30]1[CH:35]=[CH:34][C:33]([S:36]([O:17][CH2:16][C@H:9]2[O:8][C@@:7]3([C:18]4[C:4](=[CH:3][C:2]([Cl:1])=[C:20]([CH2:21][C:22]5[CH:27]=[CH:26][C:25]([CH2:28][CH3:29])=[CH:24][CH:23]=5)[CH:19]=4)[CH2:5][O:6]3)[C@H:12]([OH:13])[C@@H:11]([OH:14])[C@@H:10]2[OH:15])(=[O:38])=[O:37])=[CH:32][CH:31]=1

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 23581834(3S,3'R,4'S,5'S,6'R)-6-chloro-5-[(4-ethylphenyl)methyl]-6'-(hydroxymethyl)spiro[1H-2-benzofuran-3,2'-oxane]-3',4',5'-triol

Product 1

HCID 59013460((1S,3'R,4'S,5'S,6'R)-5-chloro-6-(4-ethylbenzyl)-3',4',5'-trihydroxy-3',4',5',6'-tetrahydro-3H-spiro[isobenzofuran-1,2'-pyran]-6'-yl)methyl 4-methylbenzenesulfonateYield 65.9%

Reagents, catalysts & solvents 1

HCID 79372,6-LutidineSolvent

Procedure

To a stirred solution of (1S,3′R,4′S,5′S,6′R)-5-chloro-6-(4-ethylbenzyl)-6′-(hydroxymethyl)-3′,4′,5′,6′-tetrahydro-3H-spiro[isobenzofuran-1,2′-pyran]-3′,4′,5′-triol (0.15 g, 0.356 mmol) in 3.5 mL of 2,6-lutidine was added p-toluenesulfonyl chloride (0.34 g, 1.78 mmol). After stirring for 21 h at ambient temperature, the solvent was distilled off. The residue was taken up with 30 mL of ethyl acetate, washed with 1 M hydrochloric acid and brine prior to drying over Na2SO4. Concentration under reduced pressure provided the crude product, which was purified by preparative TLC to give 135 mg of title compound. 1H NMR (CD3OD, 400 MHz) δ 7.61 (d, J=8.0 Hz, 2H), 7.35 (s, 1H), 7.21 (s, 1H), 7.16 (d, J=8.4 Hz, 2H), 7.11 (d, J=8.8 Hz, 4H), 5.02 (d, J=12.8 Hz, 1H), 4.97 (d, J=12.8 Hz, 1H), 4.22-4.08 (m, 4H), 3.90-3.86 (m, 1H), 3.71-3.65 (m, 2H), 3.39-3.34 (m, 1H), 2.59 (q, J=7.6 Hz, 2H), 2.33 (s, 3H), 1.18 (t, J=7.6 Hz, 3H); LC-MS (m/z) 575 [(M+1)+], 619 [(M+45)−].

Workup

  1. distillationthe solvent was distilled off
  2. washwashed with 1 M hydrochloric acid and brine
  3. dry with materialto drying over Na2SO4
  4. concentrationConcentration under reduced pressure
  5. customprovided the crude product, which
  6. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-4ef34a9604434023bbfcb9e5a37cd06f
Source dataset
uspto-grants-2010_09
Patent number
US07803778B2

Reaction notes

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