Ethanol → HCID 11779701, compound

HRID 1791980Notes

Reaction equation

HRID 1791980 reaction equation
[C:1]1([CH:6]=[O:7])([CH:4]=O)[CH2:3][CH2:2]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:20]([OH:22])[CH3:21].C([O-])([O-])O[CH2:25][CH3:26].C(=O)(O)[O-].[Na+].[C:34]1([C@@H:40]([NH2:42])[CH3:41])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[C-:43]#[N:44].[K+].S(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.CCCCCC.O>[CH2:20]([O:22][CH:6]([O:7][CH2:25][CH3:26])[C:1]1([C@H:4]([NH:42][C@H:40]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH3:41])[C:43]#[N:44])[CH2:2][CH2:3]1)[CH3:21]

Participants

13

Reactant 8

HCID 702EthanolHCID 9032Potassium CyanideHCID 758181-Phenethylamine, (-)-HCID 516892Sodium Bicarbonate2×HCID 521998p-Toluenesulfonic acid monohydrateHCID 220337631,1-CyclopropanedicarboxaldehydeHCID 23665763Sodium BisulfiteHCID 53630039Ethylorthoformate

Product 1

HCID 11779701HCID 11779701, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In toluene (20 ml) was dissolved 1,1-cyclopropane dicarboaldehyde (1.96 g, 20 mmol). Under ice cooling and stirring, a solution of p-toluenesulfonate monohydrate (19.2 mg, 0.1 mmol) in ethanol (276 mg, 6.0 mmol), and then ethyl orthoformate (3.11 g, 21 mmol) were added. The mixture was stirred at the external temperature of 40° C. for 1 hour. After addition of a saturated aqueous solution (0.3 ml) of sodium bicarbonate to the reaction mixture, (S)-1-phenylethylamine (2.67 g, 22 mmol) was added under ice cooling and stirring. At the same temperature, stirring was conducted for 30 minutes. To the reaction mixture were successively added potassium cyanide (1.43 g, 22 mmol) and sodium bisulfite (3.12 g, 30 mmol). Then, water (20 ml) was added and the mixture was stirred at 50° C. for 2 hours. A saturated aqueous solution of sodium bicarbonate was added, followed by extraction with ethyl acetate. The organic layer was washed successively with water and saturated saline, dried over anhydrous sodium sulfate, filtered, and then evaporated under reduced pressure. The yellow oil thus obtained was subjected to chromatography on a silica gel column (silica gel: 100 g, hexane:ethyl acetate=from 10:1 to 5:1), whereby a mixture (3.86 g, 63.9%) of the title compound and its diastereomer, (2R)-2-[1-(diethoxymethyl)cyclopropyl]-2-{[(1S)-1-phenylethyl]amino}acetonitrile was obtained as colorless crystals. A formation ratio of these two diastereomers was found to be 2:1 based on the integral ratio of 1H-NMR (the title compound was a main product).

Workup

  1. stirringThe mixture was stirred at the external temperature of 40° C. for 1 hour
  2. additionwas added under ice cooling
  3. stirringstirring
  4. stirringAt the same temperature, stirring
  5. stirringthe mixture was stirred at 50° C. for 2 hours
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was washed successively with water and saturated saline
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe yellow oil thus obtained

Sources & evidence

ORD record
ord-843bcf725c3343649b5e49e24eb1996e
Source dataset
uspto-grants-2006_07
Patent number
US07074837B2

Reaction notes

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