Reaction #1702088

Reaction equation

3-amino-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester, hydrochloride salt

3-benzyloxy-cyclobutanone

sodium triacetoxyborohydride

→

3-(3-benzyloxy-cyclobutylamino)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

Yield 115.7%

Solvents

DCM

ethyl acetate

Conditions

Workup

1. 1
   Washwashed sequentially with saturated aqueous sodium bicarbonate, water, and brine
2. 2
   DryingThe organic phase was dried over magnesium sulfate
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated
5. 5
   OtherThe residue was purified by silica gel chromatography (0-10% ethyl acetate:hexanes)

Procedure

A mixture of 3-amino-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester, hydrochloride salt (750 mg, 2.74 mmol) and 3-benzyloxy-cyclobutanone (2.5 g, 14.3 mmol) in DCM (40 mL) was treated with sodium triacetoxyborohydride (3.34 g, 15.8 mmol) portionwise. The mixture was stirred at room temperature for 3 hours. The solution was diluted with ethyl acetate, washed sequentially with saturated aqueous sodium bicarbonate, water, and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (0-10% ethyl acetate:hexanes). This resulted in 1.26 g (quant. yield) of 3-(3-benzyloxy-cyclobutylamino)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester as a mixture of cis- and trans-isomers.

Source