Methanol → (3-Hydroxymethyl-phenyl)-[5-isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidin-4-yl]-methanone

HRID 426192Notes

Reaction equation

HRID 426192 reaction equation
C([SiH2]OC(C)(C)C1C=C([CH:14]([C:17]2[C:22]([CH:23]([CH3:25])[CH3:24])=[C:21]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=3)[N:20]=[C:19]([O:36][CH2:37][C:38]3[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=3)[N:18]=2)C#N)C=CC=1)(C)(C)C.[H-].[Na+].[OH2:50].[C:51]1([CH3:61])[CH:56]=[CH:55][C:54](S(O)(=O)=O)=[CH:53][CH:52]=1.C[OH:63]>CN(C=O)C>[OH:50][CH2:61][C:51]1[CH:56]=[C:55]([C:14]([C:17]2[C:22]([CH:23]([CH3:24])[CH3:25])=[C:21]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)[N:20]=[C:19]([O:36][CH2:37][C:38]3[CH:39]=[CH:40][C:41]([O:44][CH3:45])=[CH:42][CH:43]=3)[N:18]=2)=[O:63])[CH:54]=[CH:53][CH:52]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 521998p-Toluenesulfonic acid monohydrateHCID 137328667[3-(tert-Butyl-dimethyl-silanyloxymethyl)-phenyl]-[5-isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidin-4-yl]-acetonitrile

Product 1

HCID 59184693(3-Hydroxymethyl-phenyl)-[5-isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidin-4-yl]-methanoneYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of [3-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-[5-isopropyl-2,6-bis-(4-methoxy-benzyloxy)-pyrimidin-4-yl]-acetonitrile (5.06 g, 7.75 mmol) in anhydrous DMF (30 ml), was added 60% sodium hydride (325 mg, 8.14 mmol). After 20 min., oxygen gas was bubbled into the reaction mixture for 3 hr. The mixture was partitioned between ether and aqueous saturated ammonium chloride solution. The ether layer was taken, washed with water twice, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was stirred with p-toluenesulfonic acid monohydrate (133 mg, 0.7 mmol) in methanol (10 ml) for 2 hr. at room temperature. The mixture was then evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ether: hexanes (from 1:1 to 2:1)) to afford 1.67 g (40%) of a white foam. 1H NMR (200 MHz, CDCl3) δ 1.15 (6H, d, J=6.8 Hz), 1.96 (1H, t, J=5.6 Hz), 2.82 (1H, m), 3.78 (3H, s), 3.82 (3H, s), 4.70 (2H, d, J=5.6 Hz), 5.28 (2H, s), 5.42 (2H, s), 6.78-6.98 (4H, m), 7.30-7.52 (5H, m), 7.61-7.79 (3H, m).

Workup

  1. customoxygen gas was bubbled into the reaction mixture for 3 hr
  2. customThe mixture was partitioned between ether and aqueous saturated ammonium chloride solution
  3. washwashed with water twice
  4. dry with materialdried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customat room temperature
  8. customThe mixture was then evaporated in vacuo
  9. customthe residue was purified by silica gel column chromatography (eluent, ether: hexanes (from 1:1 to 2:1))

Sources & evidence

ORD record
ord-a5f236dcba2e45179162452fa3200700
Source dataset
uspto-grants-2012_01
Patent number
US08106064B2

Reaction notes

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