Benzyl Bromide → (s)-Methyl 2-(4-(benzyloxymethyl)-6-methylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropanoate

HRID 1513208Notes

Reaction equation

HRID 1513208 reaction equation
[H-].[Li+].[OH:3][CH2:4][C:5]1[CH:10]=[C:9]([CH3:11])[N:8]=[C:7]([O:12][C@@H:13]([C:18]([O:31][CH3:32])([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:14]([O:16][CH3:17])=[O:15])[N:6]=1.[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>O1CCCC1.CN(C)C=O>[CH2:33]([O:3][CH2:4][C:5]1[CH:10]=[C:9]([CH3:11])[N:8]=[C:7]([O:12][C@@H:13]([C:18]([O:31][CH3:32])([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:14]([O:16][CH3:17])=[O:15])[N:6]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 62714Lithium hydrideHCID 59441450(S)-Methyl 2-(4-(hydroxymethyl)-6-methylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropanoate

Product 1

HCID 59441452(s)-Methyl 2-(4-(benzyloxymethyl)-6-methylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropanoateYield 69%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. mixture of lithium hydride (0.235 g, 29.4 mmol) in tetrahydrofuran and dimethylformamide (30 mL: 10 mL) is added the compound of Example 11 (3.0 g, 7.3 mmol) and the mixture stirred for 0.5 hr. Benzyl bromide (1.257 g, 7.3 mmol) is then added and the reaction stirred 12 hr at room temperature. The reaction is poured into ice-water (100 mL) and the quenched mixture extracted with ethyl acetate (2×100 mL). Concentration gives crude product that is purified by column chromatography on silica gel eluted with ethyl acetate-hexane (1:9) to yield the title compound (2.5 g, 69%). MS m/z 499.0 (M+.1).

Workup

  1. stirringthe reaction stirred 12 hr at room temperature
  2. extractionthe quenched mixture extracted with ethyl acetate (2×100 mL)
  3. concentrationConcentration
  4. customgives crude product that
  5. customis purified by column chromatography on silica gel
  6. washeluted with ethyl acetate-hexane (1:9)

Sources & evidence

ORD record
ord-25927e589e3d40abaa1dc3171ca0a158
Source dataset
uspto-grants-2012_07
Patent number
US08217155B2

Reaction notes

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