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

HRID 433137Notes

Reaction equation

HRID 433137 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) was 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 was heated to 50° C. for 12 h. The reaction mixture was quenched by the addition of water (500 mL). The aqueous layer was separated and extracted with dichloromethane (2×200 mL). The combined organic extracts were washed with aqueous hydrogen chloride (1.0 M, 200 mL), water (200 mL), aqueous sodium chloride (200 mL), dried (magnesium sulfate), and the solvent was removed in vacuo to provide a crude solid. Purification by flash column chromatography (silica, ethyl acetate:hexanes 2:3) gave 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 was quenched by the addition of water (500 mL)
  2. customThe aqueous layer was separated
  3. extractionextracted with dichloromethane (2×200 mL)
  4. washThe combined organic extracts were 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 was 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-4bd5f04d967448388f4bcda3057c71d4
Source dataset
uspto-grants-2003_12
Patent number
US06667322B2

Reaction notes

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