Tert-Butyl nitrite → Ethyl 5-ethylthiophene-3-carboxylate

HRID 1809077Notes

Reaction equation

HRID 1809077 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([CH2:11][CH3:12])[S:8][C:7]=1N)=[O:5])[CH3:2].N(OC(C)(C)C)=O.[Cl-].[NH4+]>C(O)C.[Cu](Br)Br>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([CH2:11][CH3:12])[S:8][CH:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 10906Tert-Butyl nitriteHCID 25517Ammonium ChlorideHCID 78263Ethyl 2-amino-5-ethyl-3-thenoate

Product 1

HCID 12588559Ethyl 5-ethylthiophene-3-carboxylateYield 52.1%

Reagents, catalysts & solvents 2

HCID 24611Copper bromide (CuBr2)CatalystHCID 702EthanolSolvent

Procedure

2-Amino-5-ethyl-thiophene-3-carboxylic acid ethyl ester (2.5 g, 12.5 mmol) was added to a suspension of t-butyl nitrite (18.8 mmol) and copper (II) bromide (15.1 mmol) in ethanol (120 mL). The reaction mixture was stirred for 15 minutes then saturated aqueous ammonium chloride (7 mL) was added and the mixture stirred for a further 15 minutes. The solvent was removed under vacuum and product partitioned between diethyl ether and water. The organic layer was dried over magnesium sulphate, filtered and the solvent removed. The product was purified by column chromatography on silica, eluting with 0%-10% ethyl acetate in cyclohexane. The fractions containing the desired product were concentrated under vacuum to give the title compound (1.2 g). 1H NMR (400 MHz, CHCl3-d): δ 7.9 (s, 1H), 7.2 (s, 1H), 3.4 (q, 2H), 2.8 (q, 2H), 1.4 (m, 6H).

Workup

  1. stirringthe mixture stirred for a further 15 minutes
  2. customThe solvent was removed under vacuum and product
  3. custompartitioned between diethyl ether and water
  4. dry with materialThe organic layer was dried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed
  7. customThe product was purified by column chromatography on silica
  8. washeluting with 0%-10% ethyl acetate in cyclohexane
  9. additionThe fractions containing the desired product
  10. concentrationwere concentrated under vacuum

Sources & evidence

ORD record
ord-e195775f0188479382a79c3ae21e6d40
Source dataset
uspto-grants-2013_01
Patent number
US08362008B2

Reaction notes

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