Azetidine → HCID 66876064, compound

HRID 1666505Notes

Reaction equation

HRID 1666505 reaction equation
CC(C)([O-])C.[Na+].Br[C:8]1[CH:9]=[CH:10][C:11]([O:14][C:15]2[CH:16]=[C:17]([CH:32]=[CH:33][CH:34]=2)[CH:18]=[C:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)=[N:12][CH:13]=1.CC(P(C(C)(C)C)C1C(C2C=CC=CC=2)=CC=CC=1)(C)C.[NH:56]1[CH2:59][CH2:58][CH2:57]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:56]1([C:8]2[CH:9]=[CH:10][C:11]([O:14][C:15]3[CH:16]=[C:17]([CH:32]=[CH:33][CH:34]=3)[CH:18]=[C:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[N:12][CH:13]=2)[CH2:59][CH2:58][CH2:57]1

Participants

7

Reactant 4

HCID 10422AzetidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 66876348tert-Butyl 4-(3-(5-bromopyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

Product 1

HCID 66876064HCID 66876064, compoundYield 23.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of sodium-tert-butoxide (0.18 g, 1.87 mmol) in toluene (2 mL) cooled to 0° C. under an inert atmosphere was added tert-butyl 4-(3-(5-bromopyridin-2-yloxy)benzylidene)piperidine-1-carboxylate (0.6 g, 1.34 mmol). The mixture was degassed for 20 min. Palladium acetate (0.02 g, 0.089 mmol) and (2-biphenyl)di-tert-butylphosphine (0.06 g, 0.2 mmol) was added and the mixture was degassed for 10 min. Azetidine (0.092 g, 1.6 mmol) was added and the reaction was heated at 85° C. for 15 h. The reaction was cooled and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate and evaporated to dryness. The residue was purified by silica gel column chromatography (5% ethyl acetate/hexane) to give the title compound (0.135 g, 23.7%). 1H NMR (500 MHz, DMSO-d6): δ 7.49 (s, 1H), 6.92 (d, J=7.7 Hz, 1H), 6.81 (m, 3H), 6.80 (d, J=8.65 Hz, 1H), 6.31 (s, 1H), 3.88 (t, J=7.15 Hz, 4H), 3.48 (m, 2H), 3.38 (m, 2H), 2.40 (m, 4H), 2.30 (m, 2H), 1.47 (s, 9H).

Workup

  1. customThe mixture was degassed for 20 min
  2. customthe mixture was degassed for 10 min
  3. temperaturethe reaction was heated at 85° C. for 15 h
  4. temperatureThe reaction was cooled
  5. custompartitioned between ethyl acetate and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. customevaporated to dryness
  9. customThe residue was purified by silica gel column chromatography (5% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b6b33b2095c04db3b63961179eaf011a
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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