4-Toluenesulfonyl chloride → Ethyl 3-[3,4-difluoro-5-((1S)-1-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)phenyl]propanoate

HRID 602036Notes

Reaction equation

HRID 602036 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[OH:12][C@@H:13]([C:16]1[CH:17]=[C:18]([CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:19]=[C:20]([F:23])[C:21]=1[F:22])[CH2:14][OH:15]>N1C=CC=CC=1>[F:23][C:20]1[CH:19]=[C:18]([CH2:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:17]=[C:16]([C@H:13]([OH:12])[CH2:14][O:15][S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=2)(=[O:9])=[O:8])[C:21]=1[F:22]

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 57470573Ethyl 3-{3-[(1S)-1,2-dihydroxyethyl]-4,5-difluorophenyl}propanoate

Product 1

HCID 86638765Ethyl 3-[3,4-difluoro-5-((1S)-1-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)phenyl]propanoateYield 81%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Conditions

Temperature
-15 °C

Procedure

p-Toluenesulfonyl chloride (12.4 g, 64.8 mmol) in pyridine (35 mL) was added dropwise over 7 min to a cooled (−10 to −20° C.) solution of ethyl 3-{3-[(1S)-1,2-dihydroxyethyl]-4,5-difluorophenyl}propanoate (17.7 g, 64.8 mmol) in pyridine (70 mL) under N2. The reaction was stirred at −10 to −20° C. for ˜4.5 h. The reaction was quenched with ice H2O and stirred overnight. The reaction mixture was diluted with H2O and extracted three times with ethyl ether. The combined organic layers were washed with 1N HCl, aq. CuSO4, and brine. The organic layer was dried over MgSO4, filtered, and concentrated. Purification by column chromatography (0-80% ethyl acetate:hexane) afforded the desired product (22.5 g, 81%) along with some recovered starting material (2.13 g).

Workup

  1. customThe reaction was quenched with ice H2O
  2. stirringstirred overnight
  3. additionThe reaction mixture was diluted with H2O
  4. extractionextracted three times with ethyl ether
  5. washThe combined organic layers were washed with 1N HCl, aq. CuSO4, and brine
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by column chromatography (0-80% ethyl acetate:hexane)

Sources & evidence

ORD record
ord-e3c9219a886c4b34a38eff1cfff894b8
Source dataset
uspto-grants-2011_03
Patent number
US07902394B2

Reaction notes

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