Cesium carbonate → (4-Isopropenyloxy-3-methoxy-phenyl)-[2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4'-piperidine]-1'-yl]methanone

HRID 1405421Notes

Reaction equation

HRID 1405421 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[C:7]([CH2:10]C(=O)C)(=O)[CH3:8].[OH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[CH2:28][CH2:27][C:26]3([N:33]([CH3:34])[CH2:32][CH2:31][N:30]4[C:35]([C:38]([F:41])([F:40])[F:39])=[CH:36][CH:37]=[C:29]34)[CH2:25][CH2:24]2)=[O:22])=[CH:17][C:16]=1[O:42][CH3:43].BrC(C)=C>Cl[Cu].C1COCC1>[C:7]([O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[CH2:24][CH2:25][C:26]3([N:33]([CH3:34])[CH2:32][CH2:31][N:30]4[C:35]([C:38]([F:41])([F:40])[F:39])=[CH:36][CH:37]=[C:29]34)[CH2:27][CH2:28]2)=[O:22])=[CH:17][C:16]=1[O:42][CH3:43])([CH3:10])=[CH2:8]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 112022-BromopropeneHCID 31261AcetylacetoneHCID 68153242(4-Hydroxy-3-methoxy-phenyl)-[2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4'-piperidine]-1'-yl]methanone

Product 1

HCID 59053471(4-Isopropenyloxy-3-methoxy-phenyl)-[2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4'-piperidine]-1'-yl]methanoneYield 16%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of Cs2CO3 (115 mg, 0.354 mmol), acetylacetone (12 μL, 0.12 mmol), CuCl (5.8 mg, 0.059 mmol) and THF (2.5 mL) in a vial was stirred at room temperature for 5 min before (4-hydroxy-3-methoxy-phenyl)-[2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-yl]methanone (100 mg, 0.236 mmol) then 2-bromoprop-1-ene (27 μL, 0.31 mmol) were added. The vial was capped and heated at 70° C. overnight. The mixture was cooled to room temperature, filtered and concentrated under reduced pressure. The residue was subjected to column chromatography (0-100% ethyl acetate/hexanes) to give (4-isopropenyloxy-3-methoxy-phenyl)-[2-methyl-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-yl]methanone (8.9 mg, 8%). ESI-MS m/z calc. 463.2, found 464.3 (M+1)+; Retention time: 1.47 minutes (3 min run). 1H NMR (400 MHz, CD3CN) δ 7.12 (d, J=1.8 Hz, 1H), 7.07 (d, J=8.0 Hz, 1H), 7.01 (dd, J=8.0, 1.8 Hz, 1H), 6.60 (d, J=3.4 Hz, 1H), 6.07 (d, J=3.7 Hz, 1H), 4.42 (s, 1H), 4.12 (dd, J=1.6, 0.9 Hz, 1H), 4.01 (t, J=6.0 Hz, 2H), 3.85 (s, 3H), 3.79 (d, J=1.7 Hz, 1H), 3.67-3.40 (m, 2H), 3.36 (t, J=5.6 Hz, 2H), 3.20 (s, 1H), 2.36 (s, 3H), 2.18 (s, 2H), 2.00 (d, J=0.7 Hz, 3H), 1.83 (s, 2H).

Workup

  1. customThe vial was capped
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-86afa00e0f60438d8c8bdc3cc1943241
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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