4-Toluenesulfonyl chloride → [(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate

HRID 47950Notes

Reaction equation

HRID 47950 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[O:11][C@@H:10]([CH2:13][OH:14])[CH2:9][CH2:8]2.[C:15]1([CH3:25])[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1.C(N(CC)C(C)C)(C)C>ClCCl.CN(C)C1C=CN=CC=1>[CH3:25][C:15]1[CH:20]=[CH:19][C:18]([S:21]([O:14][CH2:13][C@H:10]2[CH2:9][CH2:8][C:7]3[C:12](=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][CH:6]=3)[O:11]2)(=[O:23])=[O:22])=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 12114956(R)-2-Hydroxymethyl-8-methoxy-chroman

Product 1

HCID 12114957[(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonateYield 72%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of [(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methanol (5.00 g, 25.7 mmol) in dichloromethane (250 mL) is added p-toluenesulfonyl chloride (9.82 g, 51.5 mmol), 4-(dimethylamino)pyridine (0.62 g, 5.15 mmol), and N,N-diisopropylethylamine (8.32 g, 64.4 mmol) and the reaction mixture is heated to 50° C. for 12 h. The reaction mixture is quenched by the addition of water (500 mL). The aqueous layer is separated and extracted with dichloromethane (200 mL). The combined organic extracts are washed with aqueous hydrogen chloride (1.0 M, 200 mL), water (200 mL), aqueous sodium chloride (200 mL), dried (magnesium sulfate), and the solvent is removed in vacuo to provide a crude solid. Purification by flash column chromatography (silica, ethyl acetate:hexanes 2:3) provides 6.45 g (72%, 40% ee) of [(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate as a white crystalline solid. [α]D25=−20.30 (c 13.1 in chloroform, 40% ee); Rf=0.71 (silica, ethyl acetate:hexanes 2:3); mp 115-117° C.; Anal. Calcd. for C18H20O5S: C, 62.05; H, 5.79. Found: C, 61.99; H, 5.81.

Workup

  1. customThe reaction mixture is quenched by the addition of water (500 mL)
  2. customThe aqueous layer is separated
  3. extractionextracted with dichloromethane (200 mL)
  4. washThe combined organic extracts are washed with aqueous hydrogen chloride (1.0 M, 200 mL), water (200 mL), aqueous sodium chloride (200 mL)
  5. dry with materialdried (magnesium sulfate)
  6. customthe solvent is removed in vacuo
  7. customto provide a crude solid
  8. customPurification by flash column chromatography (silica, ethyl acetate:hexanes 2:3)

Sources & evidence

ORD record
ord-ed620860fa754ec9b73f6d3c8cfdba15
Source dataset
uspto-grants-2004_03
Patent number
US06700001B2

Reaction notes

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