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Potassium Phosphate, Tribasic → Methyl 5-(5,5-dimethylcyclopent-1-enyl)-2-fluoro-4-(tetrahydro-2H-pyran-2-yloxy)benzoate

HRID 2098945
Notes
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Reaction equation

HRID 2098945 reaction equation
Br[C:2]1[C:3]([O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].COC1C=CC=C(OC)[C:27]=1[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:33]=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(B2OC(C)(C)C(C)(C)O2)=CCC1>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:29][C:28]1([CH3:27])[C:33]([C:2]2[C:3]([O:13][CH:14]3[CH2:19][CH2:18][CH2:17][CH2:16][O:15]3)=[CH:4][C:5]([F:12])=[C:6]([CH:11]=2)[C:7]([O:9][CH3:10])=[O:8])=[CH:32][CH2:31][CH2:30]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 574675872-(5,5-Dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 57467603Methyl 5-bromo-2-fluoro-4-((tetrahydro-2H-pyran-2-yl)oxy)benzoate

Product 1

HCID 57467604
Methyl 5-(5,5-dimethylcyclopent-1-enyl)-2-fluoro-4-(tetrahydro-2H-pyran-2-yloxy)benzoate
Yield 261.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A stirred mixture of T22.3 (10.33 g, 31.0 mmol), ground S-Phos (2.55 g, 6.21 mmol), palladium acetate (0.70 g, 3.11 mmol), and potassium phosphate, tribasic (16.49 g, 77.7 mmol) in DMF (75 mL) and water (4 mL) was purged with argon and placed under vacuum and the process repeated three times. Before heating, 2-(5,5-dimethylcyclopent-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (T6.3) (8.96 g, 40.4 mmol) was added via syringe. The mixture was then heated at 75° C. After 21 hours, the reaction was cooled to room temperature, 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 by silica gel flash chromatography (0-10% EtOAc/hexane) to yield T22.4 (5.65 g, 52% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.63 (1H, d, J=8.6 Hz), 6.93 (1H, d, J=13.3 Hz), 5.55 (1H, t, J=2.3 Hz), 5.43 (1H, t, J=2.7 Hz), 3.90 (3H, s), 3.82 (1H, m), 3.67 (1H, m), 2.41 (2H, td, J=7.0, 2.3 Hz), 1.97 (5H, m), 1.79 (3H, m), 1.07 (6H, d, J=13.7 Hz).

Workup

  1. customwater (4 mL) was purged with argon
  2. temperatureBefore heating
  3. temperaturethe reaction was cooled to room temperature
  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 by silica gel flash chromatography (0-10% EtOAc/hexane)

Sources & evidence

ORD record
ord-86b7519694dd4c26a1cb2887c676492a
Source dataset
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08450522B2

Reaction notes

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