Methyl iodide → 1,1,1-trifluoro-2-(4-((2S)-2-(((1R,5S)-7-methoxy-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

HRID 1972488Notes

Reaction equation

HRID 1972488 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([OH:27])([CH3:26])[C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[C@@H:11]([CH2:28][N:29]2[CH:34]3[CH2:35][CH:36]([OH:38])[CH2:37][CH:30]2[CH2:31][O:32][CH2:33]3)[CH2:10]1)(=[O:8])=[O:7].[CH2:39]1COCC1.[H-].[Na+].IC>CO>[F:23][C:22]([F:25])([F:24])[C:21]([C:18]1[CH:19]=[CH:20][C:15]([N:12]2[CH2:13][CH2:14][N:9]([S:6]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)(=[O:7])=[O:8])[CH2:10][C@@H:11]2[CH2:28][N:29]2[C@H:30]3[CH2:37][CH:36]([O:38][CH3:39])[CH2:35][C@@H:34]2[CH2:33][O:32][CH2:31]3)=[CH:16][CH:17]=1)([OH:27])[CH3:26]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 70656194HCID 70656194, compound

Product 1

HCID 706556271,1,1-trifluoro-2-(4-((2S)-2-(((1R,5S)-7-methoxy-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A 25-mL round-bottomed flask was charged with 9-(((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-ol (endo) (50 mg, 0.087 mmol, Example 107) and THF (3 mL). Sodium hydride (60% dispersion in mineral oil, 34.7 mg, 0.869 mmol, Sigma-Aldrich, St. Louis, Mo.) was added at room temperature. After gas evolution had ceased iodomethane (0.054 mL, 0.87 mmol, Sigma-Aldrich, St. Louis, Mo.) was added. The reaction was stirred at room temperature for 20 min, then MeOH (20 mL) was added and then the reaction concentrated onto silica gel and purified via column chromatography (12 g silica gel, 0 to 100% hexanes in EtOAc) to give 1,1,1-trifluoro-2-(4-((2S)-2-(((1R,5S)-7-methoxy-3-oxa-9-azabicyclo[3.3.1]non-9-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (endo) (10 mg) as a mixture of two isomers.

Workup

  1. additionwas added
  2. concentrationthe reaction concentrated onto silica gel
  3. custompurified via column chromatography (12 g silica gel, 0 to 100% hexanes in EtOAc)

Sources & evidence

ORD record
ord-b718da56cf414ec5b6ef3158b7e81c05
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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