Benzyl mercaptan → 2-Benzylsulfanyl-5-(1-methanesulfonyl-piperidin-4-yloxy)-pyridine

HRID 1049042Notes

Reaction equation

HRID 1049042 reaction equation
[H-].[Na+].[CH2:3]([SH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([S:25]([CH3:28])(=[O:27])=[O:26])[CH2:21][CH2:20]2)=[CH:14][N:13]=1>CN(C=O)C.CCOC(C)=O>[CH2:3]([S:10][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([S:25]([CH3:28])(=[O:26])=[O:27])[CH2:21][CH2:20]2)=[CH:14][N:13]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 7509Benzyl mercaptanHCID 24758Sodium hydrideHCID 867218872-Chloro-5-(1-methanesulfonyl-piperidin-4-yloxy)-pyridine

Product 1

HCID 867218882-Benzylsulfanyl-5-(1-methanesulfonyl-piperidin-4-yloxy)-pyridineYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of NaH (60% dispersion in mineral oil, 413 mg, 10.32 mmol) in dry DMF (12 mL) at 0° C. was treated dropwise with benzyl mercaptan (1.21 mL, 10.32 mmol). After the addition the mixture was stirred at room temperature for 15 minutes. 2-Chloro-5-(1-methanesulfonyl-piperidin-4-yloxy)-pyridine (1.00 g, 3.44 mmol) was added and the mixture stirred at room temperature for 18 hours, heated at 80° C. for a further 8 hours and allowed to cool overnight. The mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated under vacuum. Purified by silica gel column chromatography (30-50% EtOAc in cyclohexane) to give 2-benzylsulfanyl-5-(1-methanesulfonyl-piperidin-4-yloxy)-pyridine (659 mg, 51%). 1H NMR (300 MHz, CDCl3) δ 8.20 (br s, 1H), 7.40-7.34 (m, 2H), 7.32-7.18 (s, 4H), 7.14-7.05 (m, 2H), 4.52-4.43 (m, 1H), 4.39 (s, 2H), 3.36 (t, J=5.6 Hz, 4H), 2.82 (s, 3H), 2.08-1.91 (m, 4H). LCMS (m/z, Method A) ES+ 379.1 [M+1]+.

Workup

  1. additionAfter the addition the mixture
  2. stirringthe mixture stirred at room temperature for 18 hours
  3. temperatureheated at 80° C. for a further 8 hours
  4. temperatureto cool overnight
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. customPurified by silica gel column chromatography (30-50% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-2371bc3f757a42f9a780561db7ec7f32
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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