Imidazole → (S)-methyl 2-(tert-butyldimethylsilyloxy)-3-((S)-1-methoxypropan-2-yloxy)propanoate

HRID 1098151

Reaction equation

HRID 1098151 reaction equation
Cl([O-])(=O)(=O)=O.[Mg+2].Cl([O-])(=O)(=O)=[O:8].[O:12]1[CH2:14][C@H:13]1[C:15]([O:17][CH3:18])=[O:16].[CH3:19][O:20][CH2:21][C@@H:22](O)[CH3:23].N1C=CN=C1.[C:30]([Si:34](Cl)([CH3:36])[CH3:35])([CH3:33])([CH3:32])[CH3:31]>CN(C=O)C>[Si:34]([O:8][C@@H:13]([CH2:14][O:12][C@@H:22]([CH3:23])[CH2:21][O:20][CH3:19])[C:15]([O:17][CH3:18])=[O:16])([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:36])[CH3:35]

Participants

7

Reactant 5

HCID 795ImidazoleHCID 24840Magnesium perchlorateHCID 28928tert-Butyldimethylsilyl chlorideHCID 6993459(2S)-1-methoxypropan-2-olHCID 10942355Methyl (2S)-2-oxiranecarboxylate

Product 1

HCID 59279557(S)-methyl 2-(tert-butyldimethylsilyloxy)-3-((S)-1-methoxypropan-2-yloxy)propanoateYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Magnesium perchlorate (2.79 g, 12.49 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (CAS no. 118712-39-3) (5.1 g, 49.96 mmol) and (S)-1-methoxypropan-2-ol (CAS no. 26550-55-0) (4.50 g, 49.96 mmol) at ambient temperature. The resulting suspension was stirred at 50° C. for 16 hours. The reaction mixture was diluted with DMF (50 mL) before adding 1H-imidazole (6.80 g, 99.92 mmol) and tert-butylchlorodimethylsilane (9.04 g, 59.95 mmol). The resulting solution was stirred at 40° C. for 5 hours. The reaction mixture was evaporated to dryness and re-dissolved in ethyl acetate (125 mL), and washed sequentially with water (50 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 50% ethyl acetate in isohexane to afford the product (4.52 g, 30%). 1H NMR (400 MHz, DMSO) δ 0.00 (d, 6H), 0.82 (s, 9H), 0.98 (d, 3H), 3.13-3.28 (m, 5H), 3.50-3.64 (m, 6H), 4.26-4.32 (m, 1H); m/z (ESI+) (M+H)+=307.19; HPLC tR=10.82 min.

Workup

  1. customat ambient temperature
  2. stirringThe resulting solution was stirred at 40° C. for 5 hours
  3. customThe reaction mixture was evaporated to dryness
  4. dissolutionre-dissolved in ethyl acetate (125 mL)
  5. washwashed sequentially with water (50 mL) and saturated brine (25 mL)
  6. dry with materialThe organic layer was dried (MgSO4)
  7. customevaporated
  8. customThe crude product was purified by flash silica chromatography
  9. washeluting with 0 to 50% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-04c2d16591934da0ac7f45b270d3ce7b
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Linked notes

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