Reaction #710549

Reaction equation

sodium bicarbonate

cyclobutane amine

1-[1-(4-Chlorophenyl)cyclobutyl]-3-methylbutan-1-amine

ethyl glyoxylate

sodium triacetoxyborohydride

→

54a

Ethyl 2-(1-(1-(4-chlorophenyl)cyclobutyl)-3-methylbutylamino]acetate

Solvents

—

mixture

acetic acid

DMF

Conditions

Workup

1. 1
   Extractionextracted with ethyl acetate (50 mL×3)
2. 2
   ExtractionThe combined extract
3. 3
   Washwas washed with water (50 mL)
4. 4
   Dryingdried over sodium sulfate (Na2SO4)
5. 5
   Otherevaporated
6. 6
   OtherThe residue was purified by silica gel column chromatography

Procedure

To a stirred solution of cyclobutane amine 52a (0.68 g, 0.0027 mole) and ethyl glyoxylate (50% solution in toluene) (1.02 g, 0.01 mole) in 20 mL of a mixture of solvents DMF and acetic acid (ratio, 99:1) was added sodium triacetoxyborohydride (2.11 g, 0.01 mole) portion-wise over a period of 15 minutes at room temperature. The resulting mixture was stirred for 8 hours at room temperature and the progress of the reaction was monitored by TLC. The reaction mixture was poured in to saturated sodium bicarbonate solution (50 mL) and extracted with ethyl acetate (50 mL×3). The combined extract was washed with water (50 mL), dried over sodium sulfate (Na2SO4) and evaporated. The residue was purified by silica gel column chromatography using 0-50% gradient of ethyl acetate and hexane as eluents to give pure 54a as colorless liquid in 45% (0.41 g) yield. The 1H NMR and mass spectral data are identical to the compound synthesized using the protocol described for the synthesis of 54a-e (Example 3, Scheme 7).

Source