Potassium Carbonate → tert-Butyl 2'-methyl-6'-(trifluoromethyl)-3',4'-dihydro-2'H-spiro[piperidine-4,1'-pyrrolo[1,2-a]pyrazine]-1-carboxylate

HRID 1405341ノート

反応式

HRID 1405341 の反応式
[CH3:1][N:2]1[C:10]2([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[C:6]2=[CH:7][CH:8]=[CH:9][N:5]2[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].[F:29][C:30]([F:36])([F:35])S([O-])(=O)=O.FC(F)(F)[S+]1C2C=CC=CC=2C2C=CC=CC1=2>C(#N)C>[CH3:1][N:2]1[C:10]2([CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]2)[C:6]2=[CH:7][CH:8]=[C:9]([C:30]([F:36])([F:35])[F:29])[N:5]2[CH2:4][CH2:3]1

参加物

6

反応物 4

HCID 11430Potassium CarbonateHCID 2758875TrifluoromethanesulfonateHCID 27775055-(Trifluoromethyl)dibenzothiophen-5-iumHCID 68153652tert-Butyl 2'-methyl-3',4'-dihydro-2'H-spiro[piperidine-4,1'-pyrrolo[1,2-a]pyrazine]-1-carboxylate

生成物 1

HCID 68153221tert-Butyl 2'-methyl-6'-(trifluoromethyl)-3',4'-dihydro-2'H-spiro[piperidine-4,1'-pyrrolo[1,2-a]pyrazine]-1-carboxylate収率 66%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

tert-Butyl 2-methylspiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (1.0 g, 3.27 mmol), potassium carbonate (497.7 mg, 3.60 mmol) and trifluoromethanesulfonate; 5-(trifluoromethyl)dibenzothiophen-5-ium (1.32 g, 3.27 mmol) were combined in acetonitrile (10 mL). The reaction mixture was heated at 60° C. for 16 h. The reaction was evaporated to dryness and the residue was dissolved in dichloromethane. The organics were washed with water and brine, dried over sodium sulfate and evaporated. The crude material was purified by silica gel chromatography eluting with 0-50% ethyl acetate in hexanes to give tert-butyl 2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (812 mg, 66%). ESI-MS m/z calc. 373.2, found 374.5 (M+1)+; Retention time: 1.21 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 6.52 (d, J=3.8 Hz, 1H), 5.91 (d, J=3.8 Hz, 1H), 3.98 (t, J=6.0 Hz, 2H), 3.93-3.76 (m, 2H), 3.32 (t, J=6.0 Hz, 2H), 3.26-3.08 (m, 2H), 2.36 (s, 3H), 2.11-1.99 (m, 2H), 1.81-1.65 (m, 2H), 1.47 (s, 9H).

後処理

  1. customThe reaction was evaporated to dryness
  2. dissolutionthe residue was dissolved in dichloromethane
  3. washThe organics were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated
  6. customThe crude material was purified by silica gel chromatography
  7. washeluting with 0-50% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-1fcd3406244d420ba95ad9495db79753
出典データセット
uspto-grants-2014_12
特許番号
US08916565B2

反応ノート

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