2-Methyl-3-butyn-2-ol → HCID 68818392, compound

HRID 729477Notes

Reaction equation

HRID 729477 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([O:14][C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=3[Br:22])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:29][C:30]([OH:34])([C:32]#[CH:33])[CH3:31]>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Br:22][C:16]1[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:15]=1[O:14][CH:11]1[CH2:12][CH2:13][N:8]([C:5]2[N:4]=[CH:3][C:2]([C:33]#[C:32][C:30]([CH3:31])([OH:34])[CH3:29])=[CH:7][N:6]=2)[CH2:9][CH2:10]1

Participants

7

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 11430Potassium CarbonateHCID 688207805-Bromo-2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]pyrimidine

Product 1

HCID 68818392HCID 68818392, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Into a flame-dried 25-mL sealable pressure flask equipped with a magnetic stirbar and under nitrogen was added 5-bromo-2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]pyrimidine (500 mg, 1.16 mmol), copper(I) iodide (44 mg, 0.23 mmol), Pd(PPh3)4 (100 mg, 0.09 mmol) and potassium carbonate (400 mg, 2.90 mmol). The flask was evacuated under vacuum (1 mm Hg) and backfilled with nitrogen (repeated 3 times). The solids were taken up in dimethoxyethane (4 mL) and water (4 mL) and degassed for 10 min with a stream of nitrogen. The contents of the flask where then heated to 90° C. and 2-methyl-3-butyn-2-ol (0.135 mL, 1.39 mmol) was added and the mixture heated at 90° C. for 1 h. The mixture was cooled, poured into a 250-mL separatory funnel containing water (125 mL) and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. Purification by column chromatography through silica gel, eluting with 10% EtOAc in hexanes to 50% EtOAc in hexanes as a gradient gave the desired product as a beige solid.

Workup

  1. customInto a flame-dried 25-mL sealable pressure flask equipped with a magnetic stirbar and under nitrogen
  2. customThe flask was evacuated under vacuum (1 mm Hg)
  3. customwater (4 mL) and degassed for 10 min with a stream of nitrogen
  4. temperaturethe mixture heated at 90° C. for 1 h
  5. temperatureThe mixture was cooled
  6. additionpoured into a 250-mL separatory funnel
  7. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. customthe solvent was evaporated under reduced pressure
  12. customPurification by column chromatography through silica gel
  13. washeluting with 10% EtOAc in hexanes to 50% EtOAc in hexanes as a gradient

Sources & evidence

ORD record
ord-fe4d7c5024df44c888a15fc0c7d833c3
Source dataset
uspto-grants-2009_09
Patent number
US07582633B2

Reaction notes

Loading…