Acetaldehyde → Ammonia

HRID 2225250Notes

Reaction equation

HRID 2225250 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C@H:4]([CH2:19][O:20][CH3:21])[CH2:3]1.C([BH3-])#N.[Na+].[CH3:26][C:27]([CH3:29])=O.[CH:30](=O)[CH3:31]>CO>[NH3:1].[CH2:30]([N:1]([CH:27]([CH3:29])[CH3:26])[C@@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C@H:4]([CH2:19][O:20][CH3:21])[CH2:3]1)[CH3:31]

Participants

7

Reactant 4

HCID 177Acetaldehyde3×HCID 180Acetone2×HCID 5003444Sodium cyanoborohydride4×HCID 86596950HCID 86596950, compound

Product 2

HCID 222AmmoniaHCID 86596949HCID 86596949, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Thetrifluoroacetic acid salt of benzyl (1S,2R,4R)-4-amino-2-(methoxymethyl)cyclohexylcarbamate (660 mg, assumed 1.68 mmol) was dissolved in methanol (5 mL) and treated with an excess of sodium cyanoborohydride (ca. 50-100 mg) and acetone (1 mL). The mixture was stirred overnight at rt, then treated with additional acetone and sodium cyanoborohydride. After 1 h, acetaldehyde (1 mL) was added, followed 4 h later by additional acetaldehyde and sodium cyanoborohydride. After stirring overnight at rt, additional acetaldehyde and sodium cyanoborohydride were added, followed by stirring for 3 days. The mixture was concentrated and the residue was dissolved in ethyl acetate and saturated aqueous NaHCO3. The layers were separated and the aqueous phase was extracted four times with ethyl acetate. The combined organic phases were dried over Na2SO4 and concentrated under vacuum. Purification by rotary preparative layer chromatography, eluting with 95:4:1 (v/v) dichloromethane:methanol:aqueous ammonia, provided benzyl (1S,2R,4R)-4-(ethyl(isopropyl)amino)-2-(methoxymethyl)cyclohexylcarbamate (430 mg). MS found: (M+H)+=363.4.

Workup

  1. waitAfter 1 h
  2. stirringAfter stirring overnight at rt
  3. stirringby stirring for 3 days
  4. concentrationThe mixture was concentrated
  5. dissolutionthe residue was dissolved in ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous phase was extracted four times with ethyl acetate
  8. dry with materialThe combined organic phases were dried over Na2SO4
  9. concentrationconcentrated under vacuum
  10. customPurification by rotary preparative layer chromatography
  11. washeluting with 95:4:1 (v/v) dichloromethane

Sources & evidence

ORD record
ord-ee2dd338041f4ffb8ba2cea101c4aa19
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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