Benzylamine → 3-Amino-1-benzylpyrrolidine-3-carbonitrile

HRID 1609826Notes

Reaction equation

HRID 1609826 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([NH:15]C(=O)C(O)CC(C)C)([C:13]#[N:14])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.CN1CCOCC1.C(N)C1C=CC=CC=1>C1COCC1.CN(C1C=CN=CC=1)C.CCOC(C)=O>[NH2:15][C:10]1([C:13]#[N:14])[CH2:11][CH2:12][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9]1

Participants

8

Reactant 4

HCID 7504BenzylamineHCID 79724-MethylmorpholineHCID 821294-Nitrophenyl chloroformateHCID 23589510HCID 23589510, compound

Product 1

HCID 220633693-Amino-1-benzylpyrrolidine-3-carbonitrileYield 89.4%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-hydroxy-4-methyl-pentanoic acid (1-benzyl-3-cyano-pyrrolidin-3-yl)-amide (0.315 g, 1.0 mmol) in dry THF (27 mL) was added DMAP (0.171 g, 1.4 mmol), p-nitrophenyl chloroformate (0.221 g, 1.1 mmol), and N-methylmorpholine (0. 121 mL, 1.1 mmol). The resulting mixture was allowed to stir overnight (20 h) under argon at room temperature, then treated with benzylamine (0.150 g, 1.4 mmol) and allowed to stir overnight (24 h). When the reaction was complete, the mixture was diluted with EtOAc (50 mL), then washed sequentially with saturated aq. NaHCO3 (50 mL), water and brine, dried over Na2SO4, filtered and concentrated to give 0.180 g (40% yield ) of the desired product after purification by prep-HPLC; 1H NMR (CDCl3) 7.25 (10H, m), 6.25 (1H, s), 5.4-5.1 (2H, m), 4.45 (2H, m), 3.65 (2H, m), 3.1-3.0 (1H, m), 2.98-2.57 (5H, m), 2.16 (1H, m), 1.73 (2H, m), 0.9 (6H, m). MS, m/z 449=M+1.

Workup

  1. stirringto stir overnight (24 h)
  2. washwashed sequentially with saturated aq. NaHCO3 (50 mL), water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-3db83ddcbd7f4cd68ecbead9042102dd
Source dataset
uspto-grants-2006_01
Patent number
US06982263B2

Reaction notes

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