1,2-Dichloroethane → N-[2-[(2R,4R)-4-Hydroxy-2-methyl-1-pyrrolidinyl]-2-oxoethyl]-3-(trifluoromethyl)benzamide

HRID 2367025Notes

Reaction equation

HRID 2367025 reaction equation
Cl.[CH3:2][C@H:3]1[NH:7][CH2:6][C@H:5]([OH:8])[CH2:4]1.C(N(C(C)C)CC)(C)C.[F:18][C:19]([F:34])([F:33])[C:20]1[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=1)[C:23]([NH:25][CH2:26][C:27](O)=[O:28])=[O:24].C(Cl)CCl>ClCCl.[NH4+].[Cl-].O.CO.C(OCC)(=O)C.C(OCC)(=O)C>[OH:8][C@H:5]1[CH2:6][N:7]([C:27](=[O:28])[CH2:26][NH:25][C:23](=[O:24])[C:22]2[CH:30]=[CH:31][CH:32]=[C:20]([C:19]([F:18])([F:34])[F:33])[CH:21]=2)[C@H:3]([CH3:2])[CH2:4]1

Participants

9

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 2777432((3-(Trifluoromethyl)benzoyl)amino)acetic acidHCID 67314837(3R,5R)-5-Methylpyrrolidin-3-ol hydrochloride

Product 1

HCID 57803302N-[2-[(2R,4R)-4-Hydroxy-2-methyl-1-pyrrolidinyl]-2-oxoethyl]-3-(trifluoromethyl)benzamide

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 21584119Ethylacetate methanolSolventHCID 57429219Ammonium chloride monohydrateSolvent

Procedure

(3R,5R)-5-Methylpyrrolidin-3-ol hydrochloride (1.80 g, 13 mmol) was dissolved in dichloromethane (50 mL) and diisopropylethylamine (2.1 mL, 12.0 mmol) under nitrogen. (3-Trifluoromethyl-benzoylamino)-acetic acid (2.93 g, 11.85 mmol) was added followed by EDC (3.41 g, 17.8 mmol) and the mixture was stirred at room temperature for four hours. The mixture was diluted with NH4Cl/H2O and extracted twice with ethyl acetate. The combined extracts were washed with NaHCO3/H2O and brine, dried over MgSO4, filtered and concentrated to give a dark orange oil. Chromatography on silica gel eluting with ethyl acetate to 5% methanol/ethyl acetate gave the coupled product as a pale orange solid, 3.19 g (81%, 2 steps). LC/MS (M+H)+ m/z=331.1. 1H NMR (CDCl3, major rotamer) δ 8.12 (s, 1H), 8.01 (d, 1H), 7.76 (d, 1H), 7.57 (t, 1H), 7.50 (m, 1H), 4.56 (m, 1H), 4.34 (m, 1H), 4.23 (m, 1H), 4.11 (m, 1H), 3.61 (dd, 1H), 3.51 (d, 1H), 2.71 (d, 1H), 2.17 (m, 1H), 1.81 (m, 1H), 1.32 (d, 3H).

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined extracts were washed with NaHCO3/H2O and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a dark orange oil

Sources & evidence

ORD record
ord-3946e9f375bd41faa46fd327d83aadd0
Source dataset
uspto-grants-2014_04
Patent number
US08697870B2

Reaction notes

Loading…