1,2-Dichloroethane → N-[2-[(2R,4R)-4-Hydroxy-2-methylpyrrolidin-1-yl]-2-oxoethyl}-3-(trifluoromethyl)benzamide

HRID 2367025노트

반응식

HRID 2367025 반응식
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

참가 물질

9

반응물 4

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

생성물 1

HCID 57803302N-[2-[(2R,4R)-4-Hydroxy-2-methylpyrrolidin-1-yl]-2-oxoethyl}-3-(trifluoromethyl)benzamide

시약·촉매·용매 4

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매HCID 21584119Ethylacetate methanol용매HCID 57429219Ammonium chloride monohydrate용매

실험 절차

(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).

후처리

  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

출처 및 근거

ORD 기록
ord-3946e9f375bd41faa46fd327d83aadd0
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697870B2

반응 노트

불러오는 중…