Methanesulfonyl chloride → (S)-2-Benzyl-4-(3-cyclopentyloxy4-methoxy-phenyl)-1-methanesulfonyl-piperazine

HRID 1423115Notes

Reaction equation

HRID 1423115 reaction equation
[CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>N1C=CC=CC=1>[CH2:1]([C@H:8]1[CH2:9][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:11][CH2:12][N:13]1[S:29]([CH3:28])(=[O:31])=[O:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 16725642(S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine

Product 1

HCID 23627630(S)-2-Benzyl-4-(3-cyclopentyloxy4-methoxy-phenyl)-1-methanesulfonyl-piperazineYield 94.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of the bis-hydrochloride salt of (S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine (50 mg, 0.11 mmol) in pyridine (1 mL) was treated with methanesulfonyl chloride (26 μL, 0.34 mmol) and stirred at room temperature for 16 h. The reaction mixture was evaporated and partitioned between EtOAc (2 mL) and a saturated aqueous NaHCO3 solution (2 mL). The organic component was separated, dried over MgSO4, filtered, and evaporated to an oil which was purified by silica gel flash chromatography with 30% then 40% EtOAc/hexane as eluant to afford the title compound as an oil (46 mg, 91%). 1H NMR (CDCl3) 7.36-7.23 (m, 5H), 6.78 (d, J=8.6, 1H), 6.48 (br s, 1H), 6.42 (br d, J=8.1, 1H), 4.71 (m, 1H), 4.30 (br t, 1H), 3.80 (s, 3H), 3.77 (m, 1H), 3.56-3.19 (m, 5H), 2.80-2.76 (m, 2H), 2.55 (s, 3H), 2.04-1.90 (m, 2H), 1.87-1.84 (m, 4H), 1.62-1.60 (m, 2H). LC/MS (Method A) 7.25 min, [M+1]+ 445.

Workup

  1. customThe reaction mixture was evaporated
  2. custompartitioned between EtOAc (2 mL)
  3. customThe organic component was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated to an oil which
  7. customwas purified by silica gel flash chromatography with 30%

Sources & evidence

ORD record
ord-1a0c60385328406fa5a6085772fb9d0e
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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