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 1405341Notes

Reaction equation

HRID 1405341 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-1fcd3406244d420ba95ad9495db79753
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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