Hydrochloric Acid → 2-(((tert-Butyldimethylsilyl)oxy)methyl)acrylic acid

HRID 882144Notes

Reaction equation

HRID 882144 reaction equation
[OH:1][CH2:2][C:3](=[CH2:7])[C:4]([O-:6])=[O:5].[Li+].Cl.N1C=CN=C1.[Si:15](Cl)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]>CN(C=O)C>[Si:15]([O:1][CH2:2][C:3](=[CH2:7])[C:4]([OH:6])=[O:5])([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 89613527Lithium 2-(hydroxymethyl)prop-2-enoate

Product 1

HCID 446042572-(((tert-Butyldimethylsilyl)oxy)methyl)acrylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To lithium 2-(hydroxymethyl)prop-2-enoate (926 mg, 8.57 mmol) was added DMF (17.0 mL), HCl (1.07 mL, 4 M in dioxanes, 4.28 mmol) and imidazole (700 mg, 10.3 mmol), followed by TBS-Cl (2.84 g, 18.9 mmol) at 25° C. The reaction was stirred overnight, then quenched by pouring into a separatory funnel containing water. The aqueous layer was brought to pH˜3 with 1 N HCl and was extracted with ethyl acetate (×3). The organic layers were combined and dried with Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by chromatography using MPLC using 5-80% EtOAc/hexanes. The monoprotected product was collected and concentrated in vacuo to afford a clear oil. 1H NMR (600 MHz, DMSO-D6) δ 12.67 (s, 1H), 6.13 (s, 1H), 5.80 (s, 1H), 4.31 (s, 2H), 0.92 (s, 9H), 0.09 (s, 6H).

Workup

  1. customquenched
  2. additionby pouring into a separatory funnel
  3. additioncontaining water
  4. extractionwas extracted with ethyl acetate (×3)
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by chromatography
  9. customThe monoprotected product was collected
  10. concentrationconcentrated in vacuo
  11. customto afford a clear oil

Sources & evidence

ORD record
ord-512b8cdb14a048e8b47cf13463230c96
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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