3,5-Bis(trifluoromethyl)benzoic acid → tert-butyl (3R*,4R*)-4-({[3,5-bis(trifluoromethyl)phenyl]carbonyl}amino)-3-(3,4-dichlorophenyl)piperidine-1-carboxylate

HRID 1260907ノート

反応式

HRID 1260907 の反応式
C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@@H:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C@H:14]1[C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=1.[F:34][C:35]([F:50])([F:49])[C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[C:39](O)=[O:40].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C(#N)C.O.CCN(CC)CC>[F:34][C:35]([F:49])([F:50])[C:36]1[CH:37]=[C:38]([C:39]([NH:12][C@@H:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:15][C@H:14]2[C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=2)=[O:40])[CH:42]=[C:43]([C:45]([F:46])([F:47])[F:48])[CH:44]=1

参加物

8

反応物 4

HCID 128893,5-Bis(trifluoromethyl)benzoic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86631277HCID 86631277、化合物

生成物 1

HCID 57741647tert-butyl (3R*,4R*)-4-({[3,5-bis(trifluoromethyl)phenyl]carbonyl}amino)-3-(3,4-dichlorophenyl)piperidine-1-carboxylate収率 98.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 8471Triethylamine溶媒

実験手順

To a solution of the compound (1.48 g) obtained in step 4, 3,5-bis(trifluoromethyl)benzoic acid (1.10 g) and Et3N (0.40 mL) in acetonitrile (15 mL) were added WSC.HCl (1.10 g) and HOBt (0.88 g), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10→33% ethyl acetate/hexane) to give the title compound (1.65 g, 98%) as a white powder.

後処理

  1. extractionthe resultant product was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 10→33% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-86dc5dc0c0f74da4b8ce398b6697fdc7
出典データセット
uspto-grants-2013_06
特許番号
US08470816B2

反応ノート

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