4-Methoxybenzyl alcohol → 4-Chloro-5-isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidine

HRID 426189

Reaction equation

HRID 426189 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][OH:10])=[CH:7][CH:8]=1.[H-].[Na+].[CH:13]([C:16]1[C:17]([Cl:24])=[N:18][C:19](Cl)=[N:20][C:21]=1Cl)([CH3:15])[CH3:14]>CN(C=O)C>[Cl:24][C:17]1[C:16]([CH:13]([CH3:15])[CH3:14])=[C:21]([O:10][CH2:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:20]=[C:19]([O:10][CH2:9][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[N:18]=1

Participants

5

Reactant 3

HCID 77384-Methoxybenzyl alcoholHCID 24758Sodium hydride2×HCID 2490092,4,6-Trichloro-5-isopropylpyrimidine

Product 1

HCID 591847134-Chloro-5-isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidineYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of p-methoxybenzyl alcohol (110 ml) in anhydrous DMF (50 ml) in a water bath under nitrogen atmosphere, was portionwise added 60% sodium hydride (4 g, 100 mmol). After complete reaction of sodium hydride, the mixture was cooled in an ice-water bath and 5-isopropyl-2,4,6-trichloropyrimidine (11.275 g, 50 mmol) was added. After 1 hr., the mixture was stirred for overnight at room temperature. The excess p-methoxybenzyl alcohol and DMF were distilled off in high vacuo and the residue was partitioned between ether and water. The ether layer was taken, washed with water, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo to give a crude product as a colorless syrup. The crude product was purified by silica gel column chromatography (eluent, ether:hexanes (1:9)) to afford 17 g (79%) of a white solid. m.p. 69-70° C.; 1H NMR (200 MHz, CDCl3) δ 1.23 (6H, d, J=7.0 Hz), 3.42 (1H, m), 3.81 (3H, s), 3.82 (3H, s), 5.31 (2H, s), 5.35 (2H, s), 6.87-6.92 (4H, m), 7.30-7.43 (4H, m).

Workup

  1. temperaturethe mixture was cooled in an ice-water bath
  2. distillationThe excess p-methoxybenzyl alcohol and DMF were distilled off in high vacuo
  3. customthe residue was partitioned between ether and water
  4. washwashed with water
  5. dry with materialdried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto give a crude product as a colorless syrup
  9. customThe crude product was purified by silica gel column chromatography (eluent, ether:hexanes (1:9))

Sources & evidence

ORD record
ord-8e72ac00f0a2476d9bd75c9ef1ea568e
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Linked notes

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