Methanesulfonyl chloride → di-tert-butyl (2R)-2-(((1-methylethyl)(methylsulfonyl)amino)methyl)-1,4-piperazinedicarboxylate

HRID 1972609Notes

Reaction equation

HRID 1972609 reaction equation
[CH3:1][CH:2]([NH:4][CH2:5][C@H:6]1[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9][CH2:8][N:7]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH3:3].CCN(C(C)C)C(C)C.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:3][CH:2]([N:4]([CH2:5][C@H:6]1[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:9][CH2:8][N:7]1[C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[S:36]([CH3:35])(=[O:38])=[O:37])[CH3:1]

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chloride2×HCID 81531DiisopropylethylamineHCID 66582633di-tert-butyl (2S)-2-(((1-methylethyl)amino)methyl)-1,4-piperazinedicarboxylate

Product 1

HCID 66583154di-tert-butyl (2R)-2-(((1-methylethyl)(methylsulfonyl)amino)methyl)-1,4-piperazinedicarboxylateYield 74.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A 500-mL round-bottomed flask was charged with di-tert-butyl (2S)-2-(((1-methylethyl)amino)methyl)-1,4-piperazinedicarboxylate (0.69 g, 1.9 mmol), DMAP (0.0358 g, 0.293 mmol), DIPEA (1.40 mL, 8.05 mmol) and CH2Cl2 (8 mL). To this mixture was added methanesulfonyl chloride (0.299 mL, 3.86 mmol) at room temperature. After 20 min at room temperature additional methanesulfonyl chloride (0.10 mL, 1.3 mmol) was added and stirring was continued at room temperature for an additional 1 h. The reaction mixture was partitioned between water (30 mL) and CH2Cl2 (20 mL). The aqueous phase was extracted with CH2Cl2 (30 mL) and the combined organic extracts were washed with saturated aqueous NaCl (50 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes) to afford di-tert-butyl (2R)-2-(((1-methylethyl)(methylsulfonyl)amino)methyl)-1,4-piperazinedicarboxylate (0.617 g) as a white solid.

Workup

  1. customThe reaction mixture was partitioned between water (30 mL) and CH2Cl2 (20 mL)
  2. extractionThe aqueous phase was extracted with CH2Cl2 (30 mL)
  3. washthe combined organic extracts were washed with saturated aqueous NaCl (50 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (50 g of silica gel, 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a83a211025334a57935139c5f46fdb4a
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

Loading…