HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

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

HRID 404367
Notes
Print preview

Reaction equation

HRID 404367 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 T31.3 (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 (T2.2) (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 T31.4 (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-e1ec687760b84a86bb750bdcd50bd759
Source dataset
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08748462B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes