Reaction #2200587

Reaction equation

(S)-(−)-1-phenylethylamine

(2S,3S)-2-methyl-3-tetrahydropyranyloxybutyraldehyde

(2S,3S)-2-methyl-3-benzyloxybutyraldehyde

methanol

TMSCN

→

(1R,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(S)-1′-phenylethyl]butylamine

(1S,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(S)-1′-phenylethyl]butylamine

Yield 90.0%

Solvents

dichloromethane

Conditions

Workup

1. 1
   workup.WAITat room temperature for 22 hours
2. 2
   Otherthe reaction mixture was separated in saturated NaHCO3
3. 3
   ExtractionThe aqueous phase was extracted with ether
4. 4
   Washthe ether extracts were washed with brine, they
5. 5
   Otherwere dried
6. 6
   Filtrationfiltered on a short disk of Celite and Na2SO4

Procedure

(S)-(−)-1-phenylethylamine (211 mg, 225 μl, 1.74 mmol) was added at room temperature to a solution of (2S,3S)-2-methyl-3-tetrahydropyranyloxybutyraldehyde (6) (270 mg, 1.45 mmol) in dichloromethane (6 ml), and the stirring was continued at room temperature for 2 hours. The reaction mixture was cooled to 0° C., and methanol (2 ml) and TMSCN (216 mg, 290 μl, 2.18 mmol) were successively introduced. After stirring at 0° C. for 2 hours and then at room temperature for 22 hours, the reaction mixture was separated in saturated NaHCO3 and ether. The aqueous phase was extracted with ether, the ether extracts were washed with brine, they were dried and filtered on a short disk of Celite and Na2SO4 and then evaported. Flash chromatography on a silica gel column with, as eluent, a heptane/EtOAc=10:1 then 8:1 mixture produced (1R,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(S)-1′-phenylethyl]butylamine (1R)-(17) and (1S,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(S)-1′-phenylethyl]butylamine (1S)-(17) (414 mg in total, 90%) in the ratio of about 1:3.

Source