Cyclopropylamine → (S)-2-Cyclopropylcarbamoyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1185433Notes

Reaction equation

HRID 1185433 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=C[C:19]2N(O)N=[N:22][C:20]=2[CH:21]=1.C1(N)CC1.CCN(C(C)C)C(C)C>CN(C=O)C.C(=O)([O-])O.[Na+].C(Cl)CCl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13](=[O:15])[NH:22][CH:20]1[CH2:21][CH2:19]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-

Product 1

HCID 68599173(S)-2-Cyclopropylcarbamoyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 10 g of (S)-Pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester in 953 ml of DMF, 9.2 g of HOBT, 11.5 g of EDC, 3.4 g of cyclopropylamine and 13.8 g of DIPEA was added and the reaction mixture was stirred for 16 h at RT. Then, the reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium hydrogen carbonate solution and water and dried over MgSO4. The solvents were removed under reduced pressure and the crude product was pure enough for the next reaction step.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic phase was washed with saturated aqueous sodium hydrogen carbonate solution and water
  3. dry with materialdried over MgSO4
  4. customThe solvents were removed under reduced pressure
  5. customthe crude product was pure enough for the next reaction step

Sources & evidence

ORD record
ord-744cd156121944e1a2f52b3d77f88894
Source dataset
uspto-grants-2014_03
Patent number
US08669266B2

Reaction notes

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