Tributylphosphine → 3-{4-[3-(2-Chloro-3,6-difluorophenoxy)propyl]phenyl}-2-cyano-n-cyclopropyl-n-(2,3-dichlorobenzyl)-2-methylpropanamide

HRID 561851Notes

Reaction equation

HRID 561851 reaction equation
[C:1]([C:3]([CH3:30])([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH2:28][OH:29])=[CH:22][CH:21]=1)[C:4]([N:6]([CH:16]1[CH2:18][CH2:17]1)[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=1[Cl:15])=[O:5])#[N:2].[Cl:31][C:32]1[C:37]([F:38])=[CH:36][CH:35]=[C:34]([F:39])[C:33]=1O.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>CCOCC.C1(C)C=CC=CC=1>[Cl:31][C:32]1[C:37]([F:38])=[CH:36][CH:35]=[C:34]([F:39])[C:33]=1[O:29][CH2:28][CH2:27][CH2:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][C:3]([C:1]#[N:2])([CH3:30])[C:4]([N:6]([CH:16]2[CH2:18][CH2:17]2)[CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=2[Cl:15])=[O:5])=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 27735612-Chloro-3,6-difluorophenolHCID 667613132-Cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)-3-[4-(3-hydroxypropyl)phenyl]-2-methylpropanamide

Product 1

HCID 667621493-{4-[3-(2-Chloro-3,6-difluorophenoxy)propyl]phenyl}-2-cyano-n-cyclopropyl-n-(2,3-dichlorobenzyl)-2-methylpropanamide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

2-Cyano-N-cyclopropyl-N-(2,3-dichlorobenzyl)-3-[4-(3-hydroxypropyl)phenyl]-2-methylpropanamide from the previous step (1 eq.) and 2-chloro-3,6-difluorphenol (4 eq.) were taken up in freshly deoxygenated toluene (0.05 M). To this solution was then added 1,1′-(azodicarbonyl)-dipiperidine (4 eq.) and finally tributylphosphine (4 eq.). The resulting yellow solution was heated at 80° C. for 3 h. The reaction mixture was cooled to RT, diluted with ether, and washed with 1 N aq. NaOH. The aqueous wash was back extracted with ether and the combined organic extracts were dried over MgSO4. Filtration and concentration of the filtrate in vacuo afforded a yellow semi-solid. Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex→3:2 (v/v) Hex:EtOAc) afforded the title compound as a colorless oil.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. washwashed with 1 N aq. NaOH
  3. washThe aqueous wash
  4. extractionwas back extracted with ether
  5. dry with materialthe combined organic extracts were dried over MgSO4
  6. filtrationFiltration and concentration of the filtrate in vacuo
  7. customafforded a yellow semi-solid
  8. customPurification of the crude product
  9. customthus obtained by way of flash chromatography (SiO2, Hex→3:2 (v/v) Hex:EtOAc)

Sources & evidence

ORD record
ord-0b3fc09fc9d2416bae35af9a699fd9d7
Source dataset
uspto-grants-2011_11
Patent number
US08063105B2

Reaction notes

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