Formaldehyde → tert-butyl 4,5-Dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate

HRID 611232Notes

Reaction equation

HRID 611232 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]1[CH:15]=[CH:14][S:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C=O.O.[C:19]1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]2[CH:15]=[CH:14][S:13][C:12]=2[CH2:19]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 521998p-Toluenesulfonic acid monohydrateHCID 19600076(2-Thiophen-3-YL-ethyl)-carbamic acid tert-butyl ester

Product 1

HCID 17389936tert-butyl 4,5-Dihydrothieno[2,3-c]pyridine-6(7H)-carboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1.753 g (7.711 mmol) of N-tert-butoxycarbonyl-2-(3-thienyl)ethylamine, 0.46 g (15.4 mmol) of powdered paraformaldehyde and 73 mg (0.39 mmol) of p-toluenesulfonic acid monohydrate in 150 ml of toluene was refluxed under dehydrating conditions for 0.5 hours in a Dean-Stark trap. The reaction mixture was cooled to room temperature and diluted with ethyl acetate, after which it was washed with aqueous sodium hydrogen carbonate; the organic layer was dried over anhydrous magnesium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=15/1 to 9/1) to yield the desired product.

Workup

  1. washafter which it was washed with aqueous sodium hydrogen carbonate
  2. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=15/1 to 9/1)

Sources & evidence

ORD record
ord-1bf358b0956443a6a2f5b0615cc3835d
Source dataset
uspto-grants-1999_12
Patent number
US05998433

Reaction notes

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