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

HRID 2113405Notes

Reaction equation

HRID 2113405 reaction equation
[C:1]1([C@@H:7]([NH2:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:10][C@@H:11]([C@@H:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=CC=1)[CH3:15])[CH:12]=O.C[OH:25].[Si]([C:30]#[N:31])(C)(C)C>ClCCl>[C:30]([C@H:12]([NH:9][C@H:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH3:8])[C@@H:11]([CH3:10])[C@@H:14]([O:16][CH:17]1[CH2:18][CH2:23][CH2:22][CH2:21][O:25]1)[CH3:15])#[N:31].[C:30]([C@@H:12]([NH:9][C@H:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH3:8])[C@@H:11]([CH3:10])[C@@H:14]([O:16][CH:17]1[CH2:18][CH2:23][CH2:22][CH2:21][O:25]1)[CH3:15])#[N:31]

Participants

7

Reactant 4

HCID 887MethanolHCID 758181-Phenethylamine, (-)-HCID 82115Trimethylsilyl cyanideHCID 86590269(2S,3S)-2-methyl-3-benzyloxybutyraldehyde

Product 2

HCID 11001617(1S,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(S)-1'-phenylethyl]butylamineYield 90%HCID 15541657(1R,2R,3S)-1-cyano-2-methyl-3-tetrahydropyranyloxy-N-[(S)-1'-phenylethyl]butylamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

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.

Workup

  1. waitat room temperature for 22 hours
  2. customthe reaction mixture was separated in saturated NaHCO3
  3. extractionThe aqueous phase was extracted with ether
  4. washthe ether extracts were washed with brine, they
  5. customwere dried
  6. filtrationfiltered on a short disk of Celite and Na2SO4

Sources & evidence

ORD record
ord-255e3075444643068846f4e303ca66f5
Source dataset
uspto-grants-2008_10
Patent number
US07432087B2

Reaction notes

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