Water → Methyl 3-(3,6-dihydro-2H-pyran-4-yl)-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

HRID 1662432Notes

Reaction equation

HRID 1662432 reaction equation
C1([C@H](C2C=CC=[C:11]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20](C4C=C(OC)C=CC=4F)=[C:19]([C@@H:32]4[CH2:36][CH2:35]C[C:33]4([CH3:38])C)[CH:18]=3)C=2)CC(O)=O)CC1.C[O:40][C:41]1[CH:42]=[CH:43][CH:44]=[C:45]([O:66]C)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-:68]P([O-])([O-])=O.[K+].[K+].[K+].[OH2:76]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:76]1[CH2:38][CH:33]=[C:32]([C:19]2[CH:18]=[C:17]([CH:22]=[CH:21][C:20]=2[O:66][CH:45]2[CH2:44][CH2:43][CH2:42][CH2:41][O:40]2)[C:16]([O:15][CH3:11])=[O:68])[CH2:36][CH2:35]1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57706097(3r)-3-Cyclopropyl-3-(3-(((2-((1r)-2,2-dimethylcyclopentyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)phenyl)propanoic acid

Product 1

HCID 57706658Methyl 3-(3,6-dihydro-2H-pyran-4-yl)-4-(tetrahydro-2H-pyran-2-yloxy)benzoateYield 52%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A stirred mixture of 66.6 F (1.40 g, 4.45 mmol), ground S-Phos (0.38 g, 0.920 mmol), palladium acetate (0.11 g, 0.475 mmol), 66.46B (1.40 g, 6.65 mmol), and potassium phosphate tribasic (2.48 g, 11.7 mmol) in DMF (10.0 mL) and water (0.5 mL) was purged three times with argon. The mixture was heated to 75° C. and monitored with LC-MS. After 21 hours, the reaction was cooled to room temperature and then diluted with water and extracted three times with EtOAc. The organic layers were combined and washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. The residue was purified on silica gel using 0-20% EtOAc in hexanes to afford 66.46C as a colorless oil (0.73 g, 52% yield). MS ESI (pos.) m/e: 340.9 (M+Na)+.

Workup

  1. customwas purged three times with argon
  2. temperaturethe reaction was cooled to room temperature
  3. additiondiluted with water
  4. extractionextracted three times with EtOAc
  5. washwashed twice with brine
  6. dry with materialAfter drying over anhydrous sodium sulfate and filtration
  7. customthe organic solvent was removed under reduced pressure
  8. customThe residue was purified on silica gel using 0-20% EtOAc in hexanes

Sources & evidence

ORD record
ord-4236fb732c7c476d92fac32f2a9d761e
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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