Methylamine → (R)-1-(4-Nitro-phenyl)-pyrrolidine-2-carboxylic acid methylamide

HRID 1441374Notes

Reaction equation

HRID 1441374 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:14][CH2:13][CH2:12][C@@H:11]2[C:15]([OH:17])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:18][N:19](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN>C(Cl)Cl>[CH3:18][NH:19][C:15]([C@H:11]1[CH2:12][CH2:13][CH2:14][N:10]1[C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=1)=[O:17]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 262019311-(4-Nitrophenyl)-D-proline

Product 1

HCID 68688348(R)-1-(4-Nitro-phenyl)-pyrrolidine-2-carboxylic acid methylamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (R)-1-(4-Nitro-phenyl)-pyrrolidine-2-carboxylic acid (Method 55; 1.8 g, 7.6 mmol) in DCM (50 ml) was added HATU (3.2 g, 8.4 mmol) and DIPEA (2.0 ml, 11.4 mmol). The reaction was stirred for 10 minutes before the addition of methylamine (2.0 N in THF, 5.0 ml, 15 mmol); the reaction was stirred for 1 hour before being quenched with water (50 ml). The reaction was extracted with DCM (3×100 ml), dried and solvent removed in vacuo to yield a yellow gum. Purification was achieved via column chromatography eluting with 20% EtOAc/isohexane, 60% EtOAc/isohexane and finally 100% EtOAc. The title compound was obtained as an orange gum; (1.4 g, 74%). NMR (299.954 MHz, CDCl3) 8.10 (d, 2H), 6.56 (d, 2H), 6.24 (s, 1H), 4.20 (t, 1H), 3.75 (t, 1H), 3.40 (q, 1H), 2.80 (d, 3H), 2.36-2.29 (m, 2H), 2.13-2.05 (m, 2H); m/z 250.

Workup

  1. custombefore being quenched with water (50 ml)
  2. extractionThe reaction was extracted with DCM (3×100 ml)
  3. customdried
  4. customsolvent removed in vacuo
  5. customto yield a yellow gum
  6. customPurification
  7. washeluting with 20% EtOAc/isohexane, 60% EtOAc/isohexane and finally 100% EtOAc

Sources & evidence

ORD record
ord-95cd04268cbe4dee89809271533fad8a
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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