Benzyl mercaptan → HCID 90386093, compound

HRID 1478406Notes

Reaction equation

HRID 1478406 reaction equation
[Br:1][C:2]1[C:3]([CH:9]([F:11])[F:10])=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.C([O-])([O-])=O.[K+].[K+].[C:18]1([CH2:24][SH:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C=O)C.CCOC(C)=O>[CH2:24]([S:25][C:6]1[CH:7]=[C:2]([Br:1])[C:3]([CH:9]([F:11])[F:10])=[N:4][CH:5]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH2:24]([S:25][C:2]1[C:3]([CH:9]([F:11])[F:10])=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 7509Benzyl mercaptanHCID 11430Potassium CarbonateHCID 90386101HCID 90386101, compound

Product 2

HCID 90386093HCID 90386093, compoundYield 26.1%HCID 90386321HCID 90386321, compoundYield 20.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3,5-dibromo-2-(difluoromethyl)pyridine (3.00 g, 10.5 mmol) in DMF (100 mL) was added K2CO3 (1.45 g, 10.5 mmol) at 0° C. Phenylmethanethiol (1.30 g, 10.5 mmol) in DMF (50 mL) was added through addition funnel over a period of 0.5 h and the reaction mixture was stirred at ambient temperature for 14 h. The reaction mixture was dissolved in EtOAc (300 mL) and washed with ice cold water (2×150 mL). The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by CombiFlash Isco (REDISEP®, SiO2, 12 g, 0-13% EtOAc/petroleum ether) to obtain a mixture of both regioisomers. Both regioisomers were separated by preparative HPLC (Condition B-16 described in general methods) to obtain 5-(benzylthio)-3-bromo-2-(difluoromethyl)pyridine (0.700 g, 20.3%) as a colorless liquid and 3-(benzylthio)-5-bromo-2-(difluoromethyl)pyridine (0.900 g, 26.1%) as a pale yellow liquid.

Workup

  1. washwashed with ice cold water (2×150 mL)
  2. customThe organic phase was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by CombiFlash Isco (REDISEP®, SiO2, 12 g, 0-13% EtOAc/petroleum ether)
  7. customto obtain
  8. additiona mixture of both regioisomers
  9. customBoth regioisomers were separated by preparative HPLC (Condition B-16 described in general methods)

Sources & evidence

ORD record
ord-5f8e2e9fbf1d4b738f279fb099fef454
Source dataset
uspto-grants-2016_08
Patent number
US09403834B2

Reaction notes

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