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

HRID 2367025ノート

反応式

HRID 2367025 の反応式
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

参加物

9

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 21584119Ethylacetate methanol溶媒HCID 57429219Ammonium chloride monohydrate溶媒

実験手順

(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).

後処理

  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

出典と根拠

ORDレコード
ord-3946e9f375bd41faa46fd327d83aadd0
出典データセット
uspto-grants-2014_04
特許番号
US08697870B2

反応ノート

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