Benzyl Alcohol → HCID 16042339, compound

HRID 545179Notes

Reaction equation

HRID 545179 reaction equation
C(N(CC)CC)C.[CH3:8][O:9][C:10]1[C:19]2[C:14](=[C:15]([O:20][CH3:21])[CH:16]=[CH:17][CH:18]=2)[N:13]=[C:12]([C:22]([N:24]2[CH2:29][CH2:28][C:27]3([CH2:38][C:37](=[O:39])[C:36]4[C:31](=[CH:32][CH:33]=[C:34](Br)[CH:35]=4)[O:30]3)[CH2:26][CH2:25]2)=[O:23])[CH:11]=1.[CH2:41]([OH:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.CN([CH:52]=[O:53])C>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[CH3:8][O:9][C:10]1[C:19]2[C:14](=[C:15]([O:20][CH3:21])[CH:16]=[CH:17][CH:18]=2)[N:13]=[C:12]([C:22]([N:24]2[CH2:29][CH2:28][C:27]3([CH2:38][C:37](=[O:39])[C:36]4[C:31](=[CH:32][CH:33]=[C:34]([C:52]([O:48][CH2:41][C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)=[O:53])[CH:35]=4)[O:30]3)[CH2:26][CH2:25]2)=[O:23])[CH:11]=1

Participants

8

Reactant 4

HCID 244Benzyl AlcoholHCID 6228DimethylformamideHCID 8471TriethylamineHCID 16041747HCID 16041747, compound

Product 1

HCID 16042339HCID 16042339, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

16.8 mg of palladium acetate, 83.2 mg of dppf, 0.418 mL of triethylamine, 767 mg of 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-bromospiro[chroman-2,4′-piperidin]-4-one, 0.776 mL of benzyl alcohol and 7.5 mL of DMF were stirred under a carbon monoxide atmosphere at 100° C. for 15 hours. The reaction mixture was diluted with 40 mL of ethyl acetate, and filtered through Celite. The filtrate was washed with water, dried over sodium sulfate, and concentrated. The residue was purified through silica gel chromatography (75% EtOAc/hexane) to obtain the intended compound. 1H-NMR (CDCl3) δ: 8.60 (1H, d, J=2.2 Hz), 8.21 (1H, dd, J=8.8, 2.2 Hz), 7.77 (1H, d, J=8.3 Hz), 7.49-7.31 (6H, m), 7.19 (1H, s), 7.09-7.05 (2H, m), 5.35 (2H, s), 4.62-4.55 (1H, m), 4.24-4.16 (1H, m), 4.08 (3H, s), 4.02 (3H, s), 3.60 (1H, ddd, J=13.1, 11.8, 2.9 Hz), 3.38 (1H, td, J=13.1, 2.9 Hz), 2.85 (1H, d, J=16.6 Hz), 2.79 (1H, d, J=16.6 Hz), 2.24-2.16 (1H, m), 2.10-2.02 (1H, m), 2.00-1.86 (2H, m). MS [M+H]+=567.

Workup

  1. filtrationfiltered through Celite
  2. washThe filtrate was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified through silica gel chromatography (75% EtOAc/hexane)
  6. customto obtain the intended compound

Sources & evidence

ORD record
ord-f4245be9350c483f8ee0046b91492a25
Source dataset
uspto-grants-2011_05
Patent number
US07935712B2

Reaction notes

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