3-(Chloromethyl)pyridine hydrochloride → HCID 66582346, compound

HRID 1972419Notes

Reaction equation

HRID 1972419 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]1[CH2:15][N:14]([S:16]([C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)(=[O:18])=[O:17])[CH2:13][CH2:12][N:11]1[C:24]1[CH:29]=[CH:28][C:27]([C:30]([OH:36])([CH3:35])[C:31]([F:34])([F:33])[F:32])=[CH:26][CH:25]=1)[C:2]1[CH:7]=C[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl.ClCC1C=[N:44]C=CC=1.[NH4+].[Cl-]>CN(C=O)C>[F:32][C:31]([F:34])([F:33])[C:30]([C:27]1[CH:28]=[CH:29][C:24]([N:11]2[CH2:12][CH2:13][N:14]([S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])[CH2:15][CH:10]2[CH2:9][O:8][CH2:1][C:2]2[CH:7]=[N:44][CH:5]=[CH:4][CH:3]=2)=[CH:25][CH:26]=1)([OH:36])[CH3:35]

Participants

6

Reactant 4

HCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 665825752-(4-(2-((Benzyloxy)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Product 1

HCID 66582346HCID 66582346, compoundYield 67.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A 25 ml, round-bottomed flask was charged with 1,1,1-trifluoro-2-(4-(2-(hydroxymethyl)-4-(thiophen-2-ylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (25 mg, 0.055 mmol, Example 44) and DMF (5 mL) was cooled to 0° C. To this solution was added sodium hydride (7.3 mg, 60% by weight in mineral oil, 0.18 mmol). The mixture was warmed to room temperature and stirred for 20 min. After cooling to 0° C., 3-(chloromethyl)pyridine hydrochloride (9.1 mg, 0.055 mmol, Sigma-Aldrich, St. Louis, Mo.) was added. The reaction was warmed to room temperature and stirred for 2 h. Saturated aqueous NH4Cl (0.1 mL) was added and the mixture was then purified by silica gel preparatory TLC (2:1 (5% MeOH-EtOAc) in hexanes) to yield 1,1,1-trifluoro-2-(4-(2-((3-pyridinylmethoxy)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (20 mg) as a mixture of four isomers.

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. temperatureAfter cooling to 0° C.
  3. temperatureThe reaction was warmed to room temperature
  4. stirringstirred for 2 h
  5. customthe mixture was then purified by silica gel preparatory TLC (2:1 (5% MeOH-EtOAc) in hexanes)

Sources & evidence

ORD record
ord-0aaa32905d7e419daec1e3887f87042c
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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