Piperidine → 3-[2-(trifluoromethyl)-2'-fluoro-4'-(1-piperidinyloxomethyl)benzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamide

HRID 1785730Notes

Reaction equation

HRID 1785730 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:29]=[CH:28][CH:27]=[CH:26][C:4]=1[CH:5]([O:14][CH:15]1[CH2:18][N:17]([C:19]([NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1)[C:6]1[CH:11]=[CH:10][C:9](Br)=[CH:8][C:7]=1[F:13].COCCOCC[O:39][CH3:40].C([O-])([O-])=O.[K+].[K+].[NH:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1>CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd].C1(C)C=CC=CC=1>[F:1][C:2]([F:31])([F:30])[C:3]1[CH:29]=[CH:28][CH:27]=[CH:26][C:4]=1[CH:5]([O:14][CH:15]1[CH2:18][N:17]([C:19]([NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16]1)[C:6]1[CH:11]=[CH:10][C:9]([C:40](=[O:39])[N:47]2[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]2)=[CH:8][C:7]=1[F:13]

Participants

7

Reactant 4

HCID 8082PiperidineHCID 8150DiglymeHCID 11430Potassium CarbonateHCID 99358503-[2-(trifluoromethyl)-2'-fluoro-4'-bromobenzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamide

Product 1

HCID 113760743-[2-(trifluoromethyl)-2'-fluoro-4'-(1-piperidinyloxomethyl)benzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamideYield 12%

Reagents, catalysts & solvents 2

HCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)CatalystHCID 1140TolueneSolvent

Procedure

A mixture of 3-[2-(trifluoromethyl)-2′-fluoro-4′-bromobenzhydryloxy]-N-(tert-butyl)-azetidine-1-carboxamide (115) (106 mg, 0.21 mmol), diglyme (1 mL), 4M K2CO3 (0.2 mL), toluene (1 mL), (R/S)-BINAP (12.1 mg), Herrmann's catalyst [CAS: 172418-32-5] (7.0 mg), Mo(CO)6 (26.0 mg) and piperidine (27 μL) was irradiated, with stirring, in a microwave reactor. Power was applied and varied to maintain the reaction at a temperature of 150° C. for a period of 15 min. After this time, the reaction was allowed to cool, then was filtered and evaporated. Purification by flash column chromatography [SiO2; ethyl acetate-iso-hexane (30:70→70:30)] afforded 3-[2-(trifluoromethyl)-2′-fluoro-4′-(1-piperidinyloxomethyl)benzhydryloxy]-N-(tert-butyl)azetidine-1-carboxamide (184) as a pale yellow solid (13.2 mg, 12%)

Workup

  1. customwas irradiated
  2. temperatureto maintain
  3. customthe reaction at a temperature of 150° C. for a period of 15 min
  4. temperatureto cool
  5. filtrationwas filtered
  6. customevaporated
  7. customPurification by flash column chromatography [SiO2; ethyl acetate-iso-hexane (30:70→70:30)]

Sources & evidence

ORD record
ord-c3aa7d5465d64bea8395e49a7103e3a1
Source dataset
uspto-grants-2009_03
Patent number
US07504522B2

Reaction notes

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