Dichloromethane → ((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate

HRID 1972338Notes

Reaction equation

HRID 1972338 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([S:18]([C:21]3[S:22][CH:23]=[CH:24][CH:25]=3)(=[O:20])=[O:19])[CH2:14][C@@H:13]2[CH2:26][OH:27])=[CH:8][CH:7]=1)([OH:5])[CH3:4].C(Cl)Cl.C(N(CC)CC)C.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>O>[CH3:40][S:41]([O:27][CH2:26][C@H:13]1[CH2:14][N:15]([S:18]([C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)(=[O:19])=[O:20])[CH2:16][CH2:17][N:12]1[C:9]1[CH:10]=[CH:11][C:6]([C:3]([OH:5])([CH3:4])[C:2]([F:1])([F:28])[F:29])=[CH:7][CH:8]=1)(=[O:43])=[O:42]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 665824131,1,1-trifluoro-2-(4-((2R)-2-(hydroxymethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

Product 1

HCID 86670301((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonateYield 69.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A 1-L round-bottomed flask was charged with 1,1,1-trifluoro-2-(4-((2R)-2-(hydroxymethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (42.7 g, 95 mmol), 200 mL of CH2Cl2, and triethylamine (15.18 mL, 109 mmol). After cooling to 0° C., methanesulfonyl chloride (7.75 g, 99 mmol) was added. After 5 min, another 1 equiv of triethylamine and methanesulfonyl chloride were added. The mixture was then diluted with water and extracted with CH2Cl2. The combined organics were dried (MgSO4), filtered, and concentrated. Purification by column chromatography on silica gel (0 to 50% EtOAc in hexanes) gave ((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate (35.0 g) as a light-yellow brittle foam.

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialThe combined organics were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by column chromatography on silica gel (0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-763454f819864cbca61ddd6abf1030ba
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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