Hydrochloric Acid → 5-(2-(Tert-butyldimethylsilyloxy)ethyl)-2-chlorothiophene-3-carbaldehyde

HRID 471304Notes

Reaction equation

HRID 471304 reaction equation
[C:1]([Si:5]([O:8][CH2:9][CH2:10][C:11]1[S:12][C:13]([Cl:16])=[CH:14][CH:15]=1)([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.CC1(C)CCCC(C)(C)N1.Cl.C1C[O:36][CH2:35]C1>CN(C=O)C>[Si:5]([O:8][CH2:9][CH2:10][C:11]1[S:12][C:13]([Cl:16])=[C:14]([CH:35]=[O:36])[CH:15]=1)([C:1]([CH3:4])([CH3:2])[CH3:3])([CH3:6])[CH3:7]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 130352,2,6,6-TetramethylpiperidineHCID 57989349Tert-butyl(2-(5-chlorothiophen-2-yl)ethoxy)dimethylsilaneHCID 178418339Butyllithium

Product 1

HCID 579892115-(2-(Tert-butyldimethylsilyloxy)ethyl)-2-chlorothiophene-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-butyl(2-(5-chlorothiophen-2-yl)ethoxy)dimethylsilane (0.8 g) (example 278, step a) was added dropwise over 5 min to a stirred solution of butyl lithium (2.5M in hexanes 1.7 mL) and 2,2,6,6-tetramethylpiperidine (0.73 mL) in THF (25 mL) at −78° C. The resulting mixture was stirred for 2 hrs and DMF (0.67 mL) was added. The mixture was stirred for a further 1 hr and allowed to warm to RT. The reaction was cautiously poured into HCl solution (0.5M, 200 mL) and extracted with ethyl acetate (3×100 mL). The combined organic solutions were washed with water (2×100 mL), brine (100 mL), dried over sodium sulphate, filtered and evaporated in vacuo. The resulting oil was purified by silica gel chromatography eluting with iso-hexane to 5% ether in iso-hexane gradient. The fractions containing product were combined and evaporated in vacuo to give the subtitle compound as a clear oil. Yield (0.8 g)

Workup

  1. stirringThe mixture was stirred for a further 1 hr
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe combined organic solutions were washed with water (2×100 mL), brine (100 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe resulting oil was purified by silica gel chromatography
  8. washeluting with iso-hexane to 5% ether in iso-hexane gradient
  9. additionThe fractions containing product
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-4f38f8e3b6f64a26a9c7c8c2f6b6fe41
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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