Triethylamine → HCID 68153610, compound

HRID 1405346Notes

Reaction equation

HRID 1405346 reaction equation
[F:1][C:2]([F:25])([F:24])[C:3]1[N:7]2[CH2:8][CH2:9][NH:10][C:11]3([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[C:6]2=[CH:5][CH:4]=1.CCN(CC)CC.[CH3:33][N:34]=[C:35]=[O:36]>C1COCC1>[CH3:33][NH:34][C:35]([N:10]1[C:11]2([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:13][CH2:12]2)[C:6]2=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:24])[F:25])[N:7]2[CH2:8][CH2:9]1)=[O:36]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 12228Methyl Isocyanate2×HCID 68153238HCID 68153238, compound

Product 1

HCID 68153610HCID 68153610, compoundYield 97.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To tert-butyl 6-(trifluoromethyl)spiro[3,4-dihydro-2H-pyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (600 mg, 1.67 mmol), THF (3 mL) and Et3N (698 μL, 5.01 mmol) was added methyl isocyanate (199 μL, 3.34 mmol). The mixture was allowed to stir at room temperature for 2 h. The mixture was charged with additional Et3N (698 μL, 5.01 mmol) and methyl isocyanate (199 μL, 3.34 mmol), and the reaction was stirred at room temperature for 3 d. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (40 mL) and washed with water (3×10 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to yield tert-butyl 2-(methylcarbamoyl)-6-(trifluoromethyl)spiro[3,4-dihydropyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-carboxylate (680 mg, 97%). ESI-MS m/z calc. 416.2, found 417.4 (M+1)+; Retention time: 1.73 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 7.14 (q, J=4.3 Hz, 1H), 6.56 (d, J=3.4 Hz, 1H), 6.03 (d, J=3.9 Hz, 1H), 3.88 (t, J=5.4 Hz, 2H), 3.73 (t, J=5.4 Hz, 2H), 3.69-3.55 (m, 2H), 3.23-3.03 (m, 2H), 2.78-2.62 (m, 2H), 2.56 (d, J=4.4 Hz, 3H), 1.76-1.60 (m, 2H), 1.40 (s, 9H).

Workup

  1. stirringthe reaction was stirred at room temperature for 3 d
  2. customThe solvent was evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (40 mL)
  4. washwashed with water (3×10 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4f55cb17abd646b5913e5d7e3a891119
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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