Methyl iodide → tert-Butyl 3-(methyl(thiazol-2-yl)amino)pyrrolidine-1-carboxylate

HRID 252939Notes

Reaction equation

HRID 252939 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH:6][CH:7]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8]1.[H-].[Na+].I[CH3:22].[NH4+].[OH-]>CC#N.C(Cl)(Cl)Cl.CC(=O)OCC>[CH3:22][N:6]([C:2]1[S:1][CH:5]=[CH:4][N:3]=1)[CH:7]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8]1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 14923Ammonium HydroxideHCID 24758Sodium hydrideHCID 71629653tert-Butyl 3-(thiazol-2-ylamino)pyrrolidine-1-carboxylate

Product 1

HCID 66862825tert-Butyl 3-(methyl(thiazol-2-yl)amino)pyrrolidine-1-carboxylateYield 34.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21584013Chloroform ethylacetateSolvent

Procedure

A solution of 8.73 g (32.4 mmol) of tert.-butyl 3-(thiazol-2-ylamino)pyrrolidine-1-carboxylate (synthesis described in Example 11) in MeCN (120 ml) was combined with 1.56 g (38.9 mmol, 60% strength in mineral oil) of sodium hydride and stirred for 30 min at RT. 4.04 ml (64.8 mmol) of iodomethane were then added and stirring was continued for a further 3 h at RT. After addition of a conc. aq. NH4OH soln. (30 ml), the phases were separated and the aqueous phase was extracted with EA. The collected organic phases were dried over MgSO4, filtered and evaporated under a vacuum. 3.16 g (11.2 mmol, 34%) of tert.-butyl 3-(methyl(thiazol-2-yl)amino)pyrrolidine-1-carboxylate were obtained by CC (chloroform/EA 20:1) with the residue.

Workup

  1. stirringstirring
  2. waitwas continued for a further 3 h at RT
  3. custom(30 ml), the phases were separated
  4. extractionthe aqueous phase was extracted with EA
  5. dry with materialThe collected organic phases were dried over MgSO4
  6. filtrationfiltered
  7. customevaporated under a vacuum

Sources & evidence

ORD record
ord-f27e91b0729f4fbd9c1eba3a61da3c95
Source dataset
uspto-grants-2011_01
Patent number
US07871999B2

Reaction notes

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