4-Toluenesulfonyl chloride → (2R)-3,4-dihydro-2H-benzo[h]chromen-2-ylmethyl 4-methylbenzenesulfonate

HRID 47954Notes

Reaction equation

HRID 47954 reaction equation
[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]3=2)[CH2:4][CH2:3][C@@H:2]1[CH2:15][OH:16].[C:17]1([CH3:27])[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1.C(N(CC)C(C)C)(C)C>ClCCl.CN(C)C1C=CN=CC=1>[CH3:27][C:17]1[CH:22]=[CH:21][C:20]([S:23]([O:16][CH2:15][C@H:2]2[CH2:3][CH2:4][C:5]3[C:10](=[C:9]4[CH:11]=[CH:12][CH:13]=[CH:14][C:8]4=[CH:7][CH:6]=3)[O:1]2)(=[O:25])=[O:24])=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 12146360HCID 12146360, compound

Product 1

HCID 86588254(2R)-3,4-dihydro-2H-benzo[h]chromen-2-ylmethyl 4-methylbenzenesulfonateYield 77.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (2R)-3,4-dihydro-2H-benzo[h]chromen-2-ylmethanol (0.90 g, 4.22 mmol) in dichloromethane (50 mL) is added p-toluenesulfonyl chloride (1.61 g, 8.44 mmol), 4-(dimethylamino)pyridine (0.10 g, 0.84 mmol), and N,N-diisopropylethylamine (1.20 g, 9.28 mmol) and the reaction mixture is heated to 50° C. for 12 h. The reaction mixture is quenched by the addition of water (100 mL). The aqueous layer is separated and extracted with dichloromethane (100 mL). The combined organic extracts are washed with aqueous hydrogen chloride (1.0 M, 100 mL), water (100 mL), aqueous sodium chloride (100 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 1.20 g (77%, 50% ee) of (2R)-3,4-dihydro-2H-benzo[h]chromen-2-ylmethyl 4-methylbenzenesulfonate as a white solid. [α]D25=−10.23 (c 10.16 in chloroform, 50% ee); Rf=0.68 (silica, ethyl acetate:hexanes 2:3); mp 107-111° C.; Anal. Calcd. for C21H20O4S: C, 68.46; H, 5.47. Found: C, 68.10; H, 5.27.

Workup

  1. customThe reaction mixture is quenched by the addition of water (100 mL)
  2. customThe aqueous layer is separated
  3. extractionextracted with dichloromethane (100 mL)
  4. washThe combined organic extracts are washed with aqueous hydrogen chloride (1.0 M, 100 mL), water (100 mL), aqueous sodium chloride (100 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-f9956c0cf2a94f6e82223a14846ee149
Source dataset
uspto-grants-2004_03
Patent number
US06700001B2

Reaction notes

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