Pyridine → (3S)-tert-butyl 3-(acetylthiomethyl)-4-(2-chloro-2-(3-cyano-4-fluoro-2-methylphenyl)ethyl)piperazine-1-carboxylate

HRID 2175833Notes

Reaction equation

HRID 2175833 reaction equation
[C:1]([S:4][CH2:5][C@H:6]1[N:11]([CH2:12][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[C:17]([C:22]#[N:23])[C:16]=2[CH3:24])O)[CH2:10][CH2:9][N:8]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:7]1)(=[O:3])[CH3:2].S(Cl)([Cl:34])=O.N1C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]([S:4][CH2:5][C@H:6]1[N:11]([CH2:12][CH:13]([Cl:34])[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[C:17]([C:22]#[N:23])[C:16]=2[CH3:24])[CH2:10][CH2:9][N:8]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:7]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 86727057(3S)-tert-butyl 3-(acetylthiomethyl)-4-(2-(3-cyano-4-fluoro-2-methylphenyl)-2-hydroxyethyl)piperazine-1-carboxylate

Product 1

HCID 86727058(3S)-tert-butyl 3-(acetylthiomethyl)-4-(2-chloro-2-(3-cyano-4-fluoro-2-methylphenyl)ethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3S)-tert-butyl 3-(acetylthiomethyl)-4-(2-(3-cyano-4-fluoro-2-methylphenyl)-2-hydroxyethyl)piperazine-1-carboxylate (30.8 mg, 0.0680 mmol) in toluene (0.62 mL) was added thionyl chloride (14.9 μL, 0.205 mmol). The mixture was cooled with an ice bath and then pyridine (22.1 μL, 0.273 mmol) was added dropwise. The reaction mixture was stirred at 0° C. for 20 min, and then allowed to warm to room temperature over an hour and finally heated at 70° C. for 30 min. The reaction mixture was concentrated and the residue was diluted with ethyl acetate, washed with a minimum amount of saturated sodium bicarbonate aqueous solution, and then brine. The organic layer was separated, filtered through a pad of anhydrous sodium sulfate and concentrated. Used directly in the next step.

Workup

  1. temperatureThe mixture was cooled with an ice bath
  2. temperatureto warm to room temperature over an hour
  3. temperaturefinally heated at 70° C. for 30 min
  4. concentrationThe reaction mixture was concentrated
  5. additionthe residue was diluted with ethyl acetate
  6. washwashed with a minimum amount of saturated sodium bicarbonate aqueous solution
  7. customThe organic layer was separated
  8. filtrationfiltered through a pad of anhydrous sodium sulfate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-06c5e8870c514a2eaef3b04c6f8cf280
Source dataset
uspto-grants-2015_06
Patent number
US09062070B2

Reaction notes

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