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

HRID 1972601Notes

Reaction equation

HRID 1972601 reaction equation
[CH3:1][CH:2]([CH3:26])[CH2:3][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].CCN(C(C)C)C(C)C.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:1][CH:2]([CH3:26])[CH2:3][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]([CH3:24])([CH3:23])[CH3:25])=[O:20])[S:37]([CH3:36])(=[O:39])=[O:38]

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 66582835di-tert-butyl (2S)-2-(((2-methylpropyl)amino)methyl)-1,4-piperazinedicarboxylate

Product 1

HCID 66582603di-tert-butyl (2R)-2-(((2-methylpropyl)(methylsulfonyl)amino)methyl)-1,4-piperazinedicarboxylateYield 89.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A 250-mL round-bottomed flask was charged with di-tert-butyl (2S)-2-(((2-methylpropyl)amino)methyl)-1,4-piperazinedicarboxylate (0.77 g, 2.1 mmol), DMAP (0.0287 g, 0.235 mmol) and DIPEA (1.45 mL, 8.29 mmol) and CH2Cl2 (10 mL). Methanesulfonyl chloride (0.321 mL, 4.15 mmol) was added drop wise at room temperature. The mixture was stirred for 30 min and partitioned between water (30 mL) and CH2Cl2 (20 mL). The aqueous phase was extracted with CH2Cl2 (30 mL) and the combined organic phases were washed with saturated aqueous NaCl (50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (50 g of silica gel, 10 to 70% EtOAc in hexanes) to afford di-tert-butyl (2R)-2-(((2-methylpropyl)(methylsulfonyl)amino)methyl)-1,4-piperazinedicarboxylate (0.842 g) as a white solid.

Workup

  1. custompartitioned between water (30 mL) and CH2Cl2 (20 mL)
  2. extractionThe aqueous phase was extracted with CH2Cl2 (30 mL)
  3. washthe combined organic phases were washed with saturated aqueous NaCl (50 mL)
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (50 g of silica gel, 10 to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f84c14cbe7cc4d9b913d6b2fd7238874
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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