Triphenylphosphine → 3-[4-((S)-2-{2-methyl-4-[2,2,2-trifluoro-1-(4-methoxy-benzyloxy)-1-trifluoromethyl-ethyl]-phenoxy}-3-phenyl-propoxy)-phenyl]-propionic acid methyl ester

HRID 1452700Notes

Reaction equation

HRID 1452700 reaction equation
[CH3:1][C:2]1[CH:18]=[C:17]([C:19]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)([C:24]([F:27])([F:26])[F:25])[C:20]([F:23])([F:22])[F:21])[CH:16]=[CH:15][C:3]=1[O:4][C@@H:5]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:6][OH:7].[CH3:38][O:39][C:40](=[O:50])[CH2:41][CH2:42][C:43]1[CH:48]=[CH:47][C:46](O)=[CH:45][CH:44]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.[NH4+].[Cl-]>C1COCC1>[CH3:38][O:39][C:40](=[O:50])[CH2:41][CH2:42][C:43]1[CH:44]=[CH:45][C:46]([O:7][CH2:6][C@@H:5]([O:4][C:3]2[CH:15]=[CH:16][C:17]([C:19]([O:28][CH2:29][C:30]3[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)([C:20]([F:22])([F:23])[F:21])[C:24]([F:25])([F:26])[F:27])=[CH:18][C:2]=2[CH3:1])[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:47][CH:48]=1

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 25517Ammonium ChlorideHCID 79706Benzenepropanoic acid, 4-hydroxy-, methyl esterHCID 5462977Diethyl azodicarboxylateHCID 86604230(S)-2-{2-methyl-4-[2,2,2-trifluoro-1-(4-methoxy-benzyloxy)-1-trifluoromethyl-ethyl]-phenoxy}-3-phenyl-propan-1-ol

Product 1

HCID 866042313-[4-((S)-2-{2-methyl-4-[2,2,2-trifluoro-1-(4-methoxy-benzyloxy)-1-trifluoromethyl-ethyl]-phenoxy}-3-phenyl-propoxy)-phenyl]-propionic acid methyl esterYield 79.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 320 mg (0.6 mmol) of (S)-2-{2-methyl-4-[2,2,2-trifluoro-1-(4-methoxy-benzyloxy)-1-trifluoromethyl-ethyl]-phenoxy}-3-phenyl-propan-1-ol in 5 mL of THF were added 0.14 g (0.8 mmol) of 3-(4-hydroxy-phenyl)-propionic acid methyl ester and 0.2 g (0.8 mmol) of triphenylphosphine. The mixture was cooled to 0°, was treated with 0.12 mL (0.8 mmol) of DEAD and was stirred at room temperature overnight. A solution of NH4Cl was added, the phases were separated and the inorganic one was extracted with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4), filtered and evaporated. The crude product was purified by column chromatography on silica gel with EtOAc/n-heptane 1:3 to yield 330 mg (79%) of 3-[4-((S)-2-{2-methyl-4-[2,2,2-trifluoro-1-(4-methoxy-benzyloxy)-1-trifluoromethyl-ethyl]-phenoxy}-3-phenyl-propoxy)-phenyl]-propionic acid methyl ester as a yellow oil.

Workup

  1. temperatureThe mixture was cooled to 0°
  2. customthe phases were separated
  3. extractionthe inorganic one was extracted with EtOAc
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by column chromatography on silica gel with EtOAc/n-heptane 1:3

Sources & evidence

ORD record
ord-1e691e815766486d991f0c01ec479a3d
Source dataset
uspto-grants-2009_01
Patent number
US07473705B2

Reaction notes

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