Reaction #160340

Reaction equation

5-Bromo-3-[(4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester

sodium borohydride

→

5-Bromo-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

Yield 77.0%

Solvents

methanol

—

hexanes

Conditions

Workup

1. 1
   workup.WAITthe reaction was left
2. 2
   workup.STIRRINGstirring at room temperature for 30 min
3. 3
   Otherquenched with a 10% solution of hydrochloric acid (20 ml)
4. 4
   ExtractionThe aqueous phase was extracted with ethyl acetate (3×10 mL)
5. 5
   Dryingthe combined ethyl acetate layer was dried (Na2SO4)
6. 6
   Concentrationconcentrated
7. 7
   OtherThe residue was purified by silica gel column chromatography

Procedure

5-Bromo-3-[(4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester (473 mg, 1.04 mmol) was dissolved in methanol (10.4 ml), cooled to 0° C. and treated with sodium borohydride (43 mg, 1.14 mmol). After 30 minutes of stirring at 0° C., the reaction was left stirring at room temperature for 30 min and quenched with a 10% solution of hydrochloric acid (20 ml). The aqueous phase was extracted with ethyl acetate (3×10 mL) and the combined ethyl acetate layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography using EtOAc:hexanes as eluent to furnished 5-Bromo-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (365 mg, 77% yield) as a solid. 1H NMR (CDCl3, 400 MHz): 6.82 (s, 1H), 4.56 (m, 1H), 3.82 (s, 3H), 3.45 (m, 1H), 2.08-1.72 (m, 4H), 1.75 (m, 1H), 1.68-1.23 (m, 11H), 0.98 (m, 1H), 0.80 (d, 3H), 0.68 (m, 2H).

Source