Trifluoroacetic acid → HCID 86597236, compound

HRID 967041Notes

Reaction equation

HRID 967041 reaction equation
C(OC([N:8]1[C@@H:12]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=2)[CH2:11][CH2:10][C@H:9]1[C:23](=[O:34])[NH:24][C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([O:32][CH3:33])[CH:26]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:23]([C@@H:9]2[CH2:10][CH2:11][C@H:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=3)[NH:8]2)=[O:34])=[CH:26][C:27]=1[O:32][CH3:33]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69156077HCID 69156077, compound

Product 1

HCID 86597236HCID 86597236, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(2S,5R)2-(4-Chloro-3-methoxy-phenylcarbamoyl)-5-(3,4-dimethoxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (3.48 g, 7.09 mmol) was dissolved in dichloromethane (100 ml) and cooled to 0° C. in an ice bath. TFA (30 ml) was then added slowly to the stirring solution. The reaction was allowed to stir and warm to room temperature overnight. The reaction mixture was concentrated in vacuo. The pH of the resulting residue was adjusted to 8 with 1N NaOH and the product extracted into ethyl acetate. The extract was then washed with brine solution (2×100 ml), dried over anhydrous Na2SO4 and concentrated in vacuo. The crude oil was chromatographed to afford (2S,5R)5-(3,4-dimethoxy-phenyl)-pyrrolidine-2-carboxylic acid (4-chloro-3-methoxy-phenyl)-amide (2.77 g, 7.09 mmol, 100% yield). Analysis H1 NMR (400 MHz, CDCl3): 10.02 (1H, broad s), 7.59 (1H, broad s), 7.21 (1H, d), 7.03-6.82 (4H, m) 4.52-4.30 (2H, m), 3.90 (9H, m), 2.70-1.88 (5H, m). MS (LC-MS): Calculated for C20H23ClN2O4 390.13, found 391.16 (M+H)+.

Workup

  1. temperaturewarm to room temperature overnight
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. extractionthe product extracted into ethyl acetate
  4. washThe extract was then washed with brine solution (2×100 ml)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude oil was chromatographed

Sources & evidence

ORD record
ord-b7fd6050aefa47cc980fdd48d8f41b88
Source dataset
uspto-grants-2005_10
Patent number
US06953801B2

Reaction notes

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