Hydrochloric Acid → (2R,5S)-1-Benzyl-5-(3-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-2-carboxylic acid ethyl ester

HRID 1527341Notes

Reaction equation

HRID 1527341 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:10][CH2:9][C@@H:8]([C:11]([OH:13])=O)[N:7]1[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:5])[CH3:2].[F:21][C:22]([F:32])([F:31])[O:23][C:24]1[CH:25]=[C:26]([CH:28]=[CH:29][CH:30]=1)[NH2:27].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.Cl>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:10][CH2:9][C@@H:8]([C:11](=[O:13])[NH:27][C:26]2[CH:28]=[CH:29][CH:30]=[C:24]([O:23][C:22]([F:21])([F:31])[F:32])[CH:25]=2)[N:7]1[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:5])[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 737533-(Trifluoromethoxy)anilineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68283039(2S,5R)-1-Benzyl-5-(ethoxycarbonyl)pyrrolidine-2-carboxylic acid

Product 1

HCID 68283977(2R,5S)-1-Benzyl-5-(3-trifluoromethoxy-phenylcarbamoyl)-pyrrolidine-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (2R,5S)-1-benzyl-pyrrolidine-2,5-dicarboxylic acid monoethyl ester (2 g, 7.21 mmol) in DMF (25 mL) was added 3-(trifluoromethoxy)aniline (1.53 mL, 8.65 mmol), HBTU (4.19 g, 10.8 mmol) and diisopropylethylamine (3.78 mL, 21.6 mmol). The reaction mixture was stirred at RT overnight. EtOAc and 1N HCl were added, the layers were separated and the aqueous one was back-extracted with EtOAc (×3). The combined organic extracts were washed with an aqueous solution containing 5% of NaHCO3, dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc gradient 100:0 to 80:20) to give the title compound. MS (LC/MS): 437.2 [M+H]+; tR (HPLC conditions b) 5.50 min.

Workup

  1. customthe layers were separated
  2. extractionthe aqueous one was back-extracted with EtOAc (×3)
  3. washThe combined organic extracts were washed with an aqueous solution
  4. additioncontaining 5% of NaHCO3
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc gradient 100:0 to 80:20)

Sources & evidence

ORD record
ord-6b5ceba09d0c4659bada3c89e5f33233
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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