Ethyl Acetate → N-(5-{3-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl}-2,3-dihydro-1H-inden-1-yl)propanamide

HRID 1500189ノート

反応式

HRID 1500189 の反応式
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([C:13]2([C:32]([F:35])([F:34])[F:33])[CH2:17][CH2:16][N:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[CH:23]([NH:27][C:28](=[O:31])[CH2:29][CH3:30])[CH2:22][CH2:21]4)[CH2:14]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C([O:40]C(=O)C)C.C(=O)([O-])O.[Na+]>O.C(#N)C.FC(F)(F)C(O)=O.N1C=CC=CC=1C([O-])=O.[Ag+2].N1C=CC=CC=1C([O-])=O>[F:37][C:2]([F:36])([F:1])[C:3]1[CH:4]=[C:5]([C:13]2([C:32]([F:35])([F:34])[F:33])[CH2:17][CH2:16][N:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[CH:23]([NH:27][C:28](=[O:31])[CH2:29][CH3:30])[CH2:22][CH2:21]4)[CH:14]2[OH:40])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

参加物

8

反応物 3

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 45377922N-[5-[3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl]indan-1-yl]propanamide

生成物 1

HCID 89816262N-(5-{3-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl}-2,3-dihydro-1H-inden-1-yl)propanamide収率 5.8%

試薬・触媒・溶媒 4

HCID 178524371HCID 178524371、化合物触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6422Trifluoroacetic acid溶媒

実験手順

131 mg (0.243 mmole) N-(5-{3-[3,5-bis(trifluoromethyl)phenyl]-3-(trifluoromethyl)pyrrolidin-1-yl}-2,3-dihydro-1H-inden-1-yl)propanamide (Ex. No. (II-a-963), known from WO 2010/043315, Table 6, Ex. No. 273) was dissolved in a solution of 0.6 ml water, 6 ml acetonitrile and 1.2 ml trifluoroacetic acid. At 0° C. 86 mg (0.243 mmole) silver-(II)2-pyridinecarboxylate were added in small portions until the solution has been discoloured. Immediately after decolourization ethylacetate and sodium hydrogencarbonate solution were added. The aqueous solution was extracted additionally two times with ethylacetate. The combined extracts were dried and evaporated under reduced pressure. The residue was purified by a reversed phase chromatography with a gradient acetonitrile/water to obtain 9 mg (5.8%) of the title compound as a mixture of isomers. NMR data are given for the main isomer.

後処理

  1. customAt 0° C
  2. extractionThe aqueous solution was extracted additionally two times with ethylacetate
  3. customThe combined extracts were dried
  4. customevaporated under reduced pressure
  5. customThe residue was purified by a reversed phase chromatography with a gradient acetonitrile/water

出典と根拠

ORDレコード
ord-aff3313145be4865a6dddce188cf5f4a
出典データセット
uspto-grants-2015_12
特許番号
US09206122B2

反応ノート

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