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

HRID 602046
Notes
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Reaction equation

HRID 602046 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]([CH:24](CC)[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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 57470582Ethyl 3-{3-[(1S)-1,2-dihydroxyethyl]-4,5-difluorophenyl}pentanoate

Product 1

HCID 86638765Ethyl 3-[3,4-difluoro-5-((1S)-1-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)phenyl]propanoateYield 79.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Conditions

Temperature
-15 °C

Procedure

p-Toluenesulfonyl chloride (9.03 g, 0.0474 mol) in pyridine (25 mL) was added dropwise to a cooled (−15° C.) solution of ethyl 3-{3-[(1S)-1,2-dihydroxyethyl]-4,5-difluorophenyl}pentanoate (13.02 g, 0.043 mol) in pyridine (50 mL) under N2. The reaction was stirred at −15° C. and warmed to RT overnight. The reaction mixture was quenched with H2O and extracted three times with ethyl ether. The combined ether layers were washed with 1N HCl, sat. CuSO4, and brine. The organic layer was dried over Na2SO4, filtered, and concentrated. Column chromatography (hexane:ethylacetate, 0-30%) yielded the desired product (14.68 g, 75%).

Workup

  1. temperaturewarmed to RT overnight
  2. customThe reaction mixture was quenched with H2O
  3. extractionextracted three times with ethyl ether
  4. washThe combined ether layers were washed with 1N HCl, sat. CuSO4, and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-3e21e6894a56454bad9c6c94f4cf3fa2
Source dataset
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07902394B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes