Tributylphosphine → 1-(4-chlorophenyl)-2-((2,6-difluoro-4-propylphenoxy)methyl)-3-(perfluoroethyl)-1H-pyrrole

HRID 2167392Notes

Reaction equation

HRID 2167392 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[C:9]2[CH2:17][OH:18])=[CH:4][CH:3]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH:30]=[CH:29][C:28]([C:31]([F:37])([F:36])[C:32]([F:35])([F:34])[F:33])=[C:27]2[CH2:38][OH:39])=[CH:22][CH:21]=1.[F:40][C:41]1[CH:42]=[C:43]([CH2:49][CH2:50][C:51](OCC)=O)[CH:44]=[C:45]([F:48])[C:46]=1[OH:47].C1CCN(C(N=NC(N2CCCCC2)=O)=[O:63])CC1.P(CCCC)(CCCC)CCCC>C1(C)C=CC=CC=1>[C:38]([O:39][C:43]1[CH:44]=[C:45]([F:48])[C:46]([O:18][CH2:17][C:9]2[N:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH:12]=[CH:11][C:10]=2[C:13]([F:14])([F:15])[F:16])=[C:41]([F:40])[CH:42]=1)(=[O:63])[CH2:27][CH3:28].[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([N:26]2[CH:30]=[CH:29][C:28]([C:31]([F:37])([F:36])[C:32]([F:33])([F:34])[F:35])=[C:27]2[CH2:38][O:47][C:46]2[C:45]([F:48])=[CH:44][C:43]([CH2:49][CH2:50][CH3:51])=[CH:42][C:41]=2[F:40])=[CH:24][CH:25]=1

Participants

8

Reactant 5

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 23136305Ethyl 3-(3,5-difluoro-4-hydroxyphenyl)propanoateHCID 90404801(1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrrol-2-yl)methanolHCID 90405789(1-(4-chlorophenyl)-3-(perfluoroethyl)-1H-pyrrol-2-yl)methanol

Product 2

HCID 904072621-(4-chlorophenyl)-2-((2,6-difluoro-4-propylphenoxy)methyl)-3-(perfluoroethyl)-1H-pyrroleHCID 1317329044-[[1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrrol-2-yl]methoxy]-3,5-difluorophenyl propanoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed [1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrrol-2-yl]methanol and (1-(4-chlorophenyl)-3-(perfluoroethyl)-1H-pyrrol-2-yl)methanol (200 mg, 0.73 mmol, 1.00 equiv), ethyl 3-(3,5-difluoro-4-hydroxyphenyl)propanoate (211 mg, 0.92 mmol, 1.20 equiv), ADDP (482 mg, 1.91 mmol, 2.50 equiv), PBu3 (232 mg, 1.15 mmol, 1.50 equiv) and toluene (10 mL). The resulting solution was stirred overnight at 60° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was then concentrated under vacuum. The resulting solution was diluted with diethyl ether (10 mL). The solids were filtered out and the resulting mixture was concentrated under vacuum. The resulting residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10) to yield ethyl 3-(4-[[1-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrrol-2-yl]methoxy]-3,5-difluorophenyl propanoate and 1-(4-chlorophenyl)-2-((2,6-difluoro-4-propylphenoxy)methyl)-3-(perfluoroethyl)-1H-pyrrole as yellow oil.

Workup

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was then concentrated under vacuum
  4. additionThe resulting solution was diluted with diethyl ether (10 mL)
  5. filtrationThe solids were filtered out
  6. concentrationthe resulting mixture was concentrated under vacuum

Sources & evidence

ORD record
ord-923139fd3edb4a3c8bb8f90620a90d47
Source dataset
uspto-grants-2015_06
Patent number
US09045454B2

Reaction notes

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