Potassium Carbonate → 4-Chloro-5-(2,2-diethoxyethyl)-6-phenylpyrimidine

HRID 717578Notes

Reaction equation

HRID 717578 reaction equation
Cl[C:2]1[C:7]([CH2:8][CH:9]([O:13][CH2:14][CH3:15])[O:10][CH2:11][CH3:12])=[C:6]([Cl:16])[N:5]=[CH:4][N:3]=1.[C:17]1(B(O)O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O>[Cl:16][C:6]1[C:7]([CH2:8][CH:9]([O:13][CH2:14][CH3:15])[O:10][CH2:11][CH3:12])=[C:2]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=[CH:4][N:5]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 197943054,6-Dichloro-5-(2,2-diethoxyethyl)pyrimidine

Product 1

HCID 898151274-Chloro-5-(2,2-diethoxyethyl)-6-phenylpyrimidineYield 63.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

The 4,6-dichloro-5-(2,2-diethoxyethyl)pyrimidine (1.1 g), phenyl boronic acid (500 mg) and potassium carbonate (556 mg) were dissolved in toluene (15 mL) and water (1.5 mL). The reaction mixture was degassed with nitrogen for 30 minute and then Pd(PPh3)4 (230 mg) was added. The reaction mixture was again degassed with nitrogen for 20 minutes before heated to 100° C. for 3 hours in a sealed tube. The reaction mixture was filtered through a celite pad and washed with ethyl acetate (2×20 mL). The combined filtrate was washed with water (10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography using EtOAc/hexane (0.5:9.5) as eluent to afford 4-chloro-5-(2,2-diethoxyethyl)-6-phenylpyrimidine (800 mg) as colorless viscous liquid. 1H NMR (DMSO-d6): δ 1.07-1.10 (t, 6H), 3.21-3.23 (d, 2H), 3.32-3.36 (q, 2H), 3.37-4.00 (q, 2H), 4.79-4.81 (t, 1H), 7.47-7.49 (m, 3H), 7.63-7.66 (m, 2H), 8.91 (s, 1H).

Workup

  1. customThe reaction mixture was degassed with nitrogen for 30 minute
  2. additionPd(PPh3)4 (230 mg) was added
  3. customThe reaction mixture was again degassed with nitrogen for 20 minutes
  4. filtrationThe reaction mixture was filtered through a celite pad
  5. washwashed with ethyl acetate (2×20 mL)
  6. washThe combined filtrate was washed with water (10 mL) and brine (10 mL)
  7. dry with materialThe organic layer was dried over anhydrous Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-bf4eb33386f2450d96ff54c391a7dcf5
Source dataset
uspto-grants-2015_11
Patent number
US09193725B2

Reaction notes

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