Pyridine → (E)-1-methyl-2-oxo-1'-(3-(2-(trifluoromethyl) phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carbonitrile

HRID 390173Notes

Reaction equation

HRID 390173 reaction equation
FC(F)(F)C(OC(=O)C(F)(F)F)=O.[CH3:14][N:15]1[C:42]2[C:37](=[CH:38][C:39]([C:43]([NH2:45])=O)=[CH:40][CH:41]=2)[C:17]2([CH2:22][CH2:21][N:20]([C:23](=[O:36])/[CH:24]=[CH:25]/[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([F:35])([F:34])[F:33])[CH2:19][CH2:18]2)[C:16]1=[O:46].N1C=CC=CC=1>O1CCOCC1.O>[CH3:14][N:15]1[C:42]2[C:37](=[CH:38][C:39]([C:43]#[N:45])=[CH:40][CH:41]=2)[C:17]2([CH2:22][CH2:21][N:20]([C:23](=[O:36])/[CH:24]=[CH:25]/[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([F:35])([F:33])[F:34])[CH2:19][CH2:18]2)[C:16]1=[O:46]

Participants

6

Reactant 3

HCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 58295665(E)-1-methyl-2-oxo-1'-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carboxamide

Product 1

HCID 58295783(E)-1-methyl-2-oxo-1'-(3-(2-(trifluoromethyl) phenyl)acryloyl)spiro[indoline-3,4'-piperidine]-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of trifluoroacetic anhydride (34 mg, 0.157 mmol) in dioxane (4 mL) was added dropwise to a stirred, ice-cooled solution of (E)-1-methyl-2-oxo-1′-(3-(2-(trifluoromethyl)phenyl)acryloyl)spiro[indoline-3,4′-piperidine]-5-carboxamide (60 mg, 0.131 mmol) and pyridine (60 mg, 0.262 mmol). The reaction mixture was stirred at rt overnight. The mixture was diluted with water and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated to afford the crude product. After purification by preparative HPLC, (E)-1-methyl-2-oxo-1′-(3-(2-(trifluoromethyl) phenyl)acryloyl)spiro[indoline-3,4′-piperidine]-5-carbonitrile was obtained (2.04 mg, 4%). 1H NMR: (400 MHz, CDCl3): δ=1.85 (m, 4H), 3.20 (m, 3H), 3.80-3.90 (m, 2H), 4.10 (m, 1H), 4.35 (m, 1H), 6.75 (m, 1H), 6.85 (m, 1H), 7.40 (m, 2H), 7.50 (m, 1H), 7.55 (m, 1H) 7.65 (m, 2H), 7.90 (m, 1H).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customto afford the crude product
  5. customAfter purification by preparative HPLC

Sources & evidence

ORD record
ord-f008275bae6041bbba3df741e83643dc
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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