1,2-Dichloroethane → N-{1-cyano-2-[(phenylmethyl)oxy]ethyl}propanamide

HRID 1874867Notes

Reaction equation

HRID 1874867 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C-:12]#[N:13].[Na+].[Cl-].[NH4+:16].[C:17]([OH:21])(=O)[CH2:18][CH3:19].C(Cl)CCl>[OH-].[NH4+].CN(C1C=CN=CC=1)C.O>[C:12]([CH:10]([NH:16][C:17](=[O:21])[CH2:18][CH3:19])[CH2:9][O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)#[N:13]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 1032Propionic AcidHCID 8929Sodium CyanideHCID 25517Ammonium ChlorideHCID 108989(Phenylmethoxy)acetaldehyde

Product 1

HCID 59451375N-{1-cyano-2-[(phenylmethyl)oxy]ethyl}propanamideYield 78%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 14923Ammonium HydroxideSolvent

Procedure

Benzyloxyacetaldehyde (3.0 g, 20.0 mmol) was added dropwise to a stirred solution of sodium cyanide (1.22 g, 24.9 mmol) and ammonium chloride (1.58 g, 29.5 mmol) in 25% ammonium hydroxide (9.6 mL). The solution was stirred at RT for 48 h, then extracted with CH2Cl2 (40 mL). The organic extract was washed with brine, dried (Na2SO4) and filtered. Propionic acid (1.5 g, 20.0 mmol), EDC (5.7 g, 30.0 mmol) and DMAP (610 mg, 5 mmol) were added to the filtrate and the solution was stirred for 12 h at RT. Water was added (20 mL) and the organic phase was separated and washed with 1N HCl (20 mL), dried (Na2SO4), filtered and concentrated. The residue was purified by silica gel flash column chromatography (0-50% EtOAc:hexanes) to give the title compound (3.62 g, 78%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.32-7.43 (m, 5H), 6.09 (br. s., 1H), 5.08-5.13 (m, 1H), 4.59-4.69 (ABq, 2 H), 3.66 (ABq, 2H), 2.25 (qd, 2H), 1.17 (t, 3H). ES-LCMS: m/z 233.0 (M+H).

Workup

  1. extractionextracted with CH2Cl2 (40 mL)
  2. extractionThe organic extract
  3. washwas washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. stirringthe solution was stirred for 12 h at RT
  7. customthe organic phase was separated
  8. washwashed with 1N HCl (20 mL)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by silica gel flash column chromatography (0-50% EtOAc:hexanes)

Sources & evidence

ORD record
ord-1f95db16b1694a4c8f977f0c21a2660e
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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