Sodium Sulfite → ethyl (3S)-3-{[(2-chloro-4-fluorophenyl)amino]sulfanyl}-3,6-dihydro-2H-pyran-4-carboxylate

HRID 1397201Notes

Reaction equation

HRID 1397201 reaction equation
[SH:1][C@H:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][CH2:5][O:4][CH2:3]1.ClOC(C)(C)C.[Cl:19][C:20]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:21]=1[NH2:22].S([O-])([O-])=O.[Na+].[Na+]>ClCCl>[Cl:19][C:20]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:21]=1[NH:22][S:1][C@H:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][CH2:5][O:4][CH2:3]1

Participants

6

Reactant 4

HCID 24437Sodium SulfiteHCID 75013Benzenamine, 2-chloro-4-fluoro-HCID 521297Tert-Butyl hypochloriteHCID 86676958ethyl (3S)-3-sulfanyl-3,6-dihydro-2H-pyran-4-carboxylate

Product 1

HCID 86676959ethyl (3S)-3-{[(2-chloro-4-fluorophenyl)amino]sulfanyl}-3,6-dihydro-2H-pyran-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution (400 mL) of ethyl (3S)-3-sulfanyl-3,6-dihydro-2H-pyran-4-carboxylate (14.5 g) in dichloromethane was added dropwise tert-butyl hypochlorite (10 mL) at −78° C. After stirring for 30 min, 2-chloro-4-fluoroaniline (23 mL) was added dropwise at −78° C. The reaction mixture was stirred for 1 hr, and the reaction was discontinued with 5% aqueous sodium sulfite solution (300 mL). After extraction with dichloromethane (300 mL), the extract was washed with water, and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography (hexane/ethyl acetate=15:1→5:1) to give the title compound as a crude product (20.0 g, 96.3% ee). This product was crystallized from diisopropyl ether/hexane (120 mL, 1:5) to give the title compound (12.3 g, 62%) as white crystals.

Workup

  1. stirringThe reaction mixture was stirred for 1 hr
  2. extractionAfter extraction with dichloromethane (300 mL)
  3. washthe extract was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationAfter concentration under reduced pressure

Sources & evidence

ORD record
ord-8514da31e6444de3a83629c5f963cc04
Source dataset
uspto-grants-2014_12
Patent number
US08901171B2

Reaction notes

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