Potassium Phosphate, Tribasic → Tert-butyl 2-hydroxy-6-[({4'-[(methoxycarbonyl)methyl]-3'-methoxy-1,1'-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate

HRID 2076626Notes

Reaction equation

HRID 2076626 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2[C:22]2[C:27]([O:28][CH3:29])=[CH:26][CH:25]=[CH:24][C:23]=2OC)CCCCC1.Cl[C:39]1[CH:44]=[CH:43][C:42]([CH2:45][C:46]([O:48][CH3:49])=[O:47])=[C:41]([O:50][CH3:51])[CH:40]=1.[OH:52][C:53]1[C:65]([C:66]([F:69])([F:68])[F:67])=[C:64](COC2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)[CH:63]=[CH:62][C:54]=1[C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[OH:52][C:53]1[C:65]([C:66]([F:69])([F:67])[F:68])=[CH:64][CH:63]=[C:62]([CH2:29][O:28][C:27]2[CH:22]=[CH:23][C:24]([C:39]3[CH:44]=[CH:43][C:42]([CH2:45][C:46]([O:48][CH3:49])=[O:47])=[C:41]([O:50][CH3:51])[CH:40]=3)=[CH:25][CH:26]=2)[C:54]=1[C:55]([O:57][C:58]([CH3:59])([CH3:60])[CH3:61])=[O:56]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 67119177Tert-butyl 2-hydroxy-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}-3-(trifluoromethyl)benzoateHCID 85739232Methyl 2-(4-chloro-2-methoxyphenyl)acetate

Product 1

HCID 67119238Tert-butyl 2-hydroxy-6-[({4'-[(methoxycarbonyl)methyl]-3'-methoxy-1,1'-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoateYield 457.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

After tripotassium phosphate (127 mg, 0.60 mmol), palladium acetate (8 mg, 0.04 mmol) and 2-(dicyclohexylphosphino)-2′,6′-dimethoxy-1,1′-biphenyl (S-PHOS) (16 mg, 0.04 mmol) were added to a solution of methyl (4-chloro-2-methoxyphenyl)acetate (43 mg, 0.2 mmol) obtained in Example (24-1) and tert-butyl 2-hydroxy-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]methyl}-3-(trifluoromethyl)benzoate (100 mg, 0.2 mmol) obtained in Example (22-4) in toluene (2.0 ml), the mixture was stirred at 70° C. for 4 hours. After the temperature of the reaction mixture was returned to room temperature, the mixture was poured into water and extracted with ethyl acetate (three times). The organic layer was successively washed with water (twice) and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=2/1) to give tert-butyl 2-hydroxy-6-[({4′-[(methoxycarbonyl)methyl]-3′-methoxy-1,1′-biphenyl-4-yl}oxy)methyl]-3-(trifluoromethyl)benzoate (100 mg, yield: 60%).

Workup

  1. customwas returned to room temperature
  2. extractionextracted with ethyl acetate (three times)
  3. washThe organic layer was successively washed with water (twice) and a saturated aqueous NaCl solution
  4. dry with materialdried with anhydrous sodium sulfate
  5. customThe residue obtained
  6. customby removing the solvent under reduced pressure
  7. customwas purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-6fc1fda48e5f41e6b4bd20a732a9b081
Source dataset
uspto-grants-2011_04
Patent number
US07923573B2

Reaction notes

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