2-Bromopyrimidine → 3-[4-(2-Pyrimidinyl)phenyl]-2-propyn-1-ol

HRID 2416538Notes

Reaction equation

HRID 2416538 reaction equation
Br[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)(O)[O-].[Na+].[OH:13][CH2:14][C:15]#[C:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1>COCCOC.O.C(Cl)Cl.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>[N:3]1[CH:4]=[CH:5][CH:6]=[N:7][C:2]=1[C:20]1[CH:21]=[CH:22][C:17]([C:16]#[C:15][CH2:14][OH:13])=[CH:18][CH:19]=1

Participants

8

Reactant 3

HCID 783452-BromopyrimidineHCID 516892Sodium BicarbonateHCID 22630943[4-(3-hydroxy-1-propynyl)phenyl]boronic Acid

Product 1

HCID 226311353-[4-(2-Pyrimidinyl)phenyl]-2-propyn-1-olYield 79%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 2-bromopyrimidine (1.00 g, 6.29 mmol) and Pd(Ph3P)4 (220 mg, 0.19 mmol) in ethylene glycol dimethyl ether (25 mL) was stirred for 10 min, a slurry of sodium bicarbonate (1.58 g, 18.81 mmol) and [4-(3-hydroxy-1-propynyl)phenyl]boronic acid (1.32 g, 7.50 mmol, prepared as described in Reference Example 235) in water (25 mL) was added, and the mixture was heated to reflux for 4 h. The cooled reaction mixture was diluted with methylene chloride (100 mL) and washed with water (100 mL). The aqueous layer was extracted with dichloromethane (25 mL) and the combined organic layers were dried (MgSO4) and concentrated. Purification by chromatography (SiO2, 3:2 hexane/ethyl acetate) provided 1.04 g (79%) of the title compound as a yellow solid. MS 211 (M+H)+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 4 h
  3. customThe cooled reaction mixture
  4. washwashed with water (100 mL)
  5. extractionThe aqueous layer was extracted with dichloromethane (25 mL)
  6. dry with materialthe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated
  8. customPurification by chromatography (SiO2, 3:2 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-98cbe00ca551436bb96fbe16248d5f21
Source dataset
uspto-grants-2004_11
Patent number
US06825170B2

Reaction notes

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