3-Nitrobenzaldehyde → 4-(3-Nitrobenzyl)morpholine

HRID 2086078Notes

Reaction equation

HRID 2086078 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1>CO.C([BH3-])#N.[Zn+2].C([BH3-])#N>[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH2:7][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)([O-:3])=[O:2]

Participants

5

Reactant 2

HCID 74493-NitrobenzaldehydeHCID 8083Morpholine

Product 1

HCID 7832314-(3-Nitrobenzyl)morpholine

Reagents, catalysts & solvents 2

HCID 131724416HCID 131724416, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 3-nitrobenzaldehyde (30 g, 0.2 mol) in methanol (150 ml) was treated with morpholine and the resulting orange solution cooled to 0° C. The solution of zinc cyanoborohydride prepared above was then introduced by means of a double-ended needle and the reaction stirred to ambient temperature over 16 hours. The reaction was filtered and the filtrate evaporated to dryness. The residue was dissolved in diethyl ether (600 ml) and washed with 1N hydrochloric acid (1 l). The organic layer (containing 3-nitrobenzyl alcohol) was discarded. The aqueous layer was made basic with 4N sodium hydroxide and extracted with diethyl ether (750 ml). The organic layer was dried over anhydrous sodium sulphate, filtered and pre-adsorbed on to silica. Purification by dry flash chromatography eluting with dichloromethane/methanol/0.880 NH3 (95:4.5:0.5) gave 4-(3-nitrobenzyl)morpholine as a pale yellow oil which crystallised on standing (22.2 g, 50%). δH (360 MHz, CDCl3) 2.45-2.48 (4H, m), 3.59 (2H, s), 3.71-3.74 (4H, m), 7.49 (1H, t, J 8), 7.68 (1H, d, J 8), 8.12 (1H, d, J 8), 8.22 (1H, s).

Workup

  1. additionwas then introduced by means of a double-ended needle
  2. filtrationThe reaction was filtered
  3. customthe filtrate evaporated to dryness
  4. dissolutionThe residue was dissolved in diethyl ether (600 ml)
  5. washwashed with 1N hydrochloric acid (1 l)
  6. additionThe organic layer (containing 3-nitrobenzyl alcohol)
  7. extractionextracted with diethyl ether (750 ml)
  8. dry with materialThe organic layer was dried over anhydrous sodium sulphate
  9. filtrationfiltered and pre-adsorbed on to silica
  10. customPurification
  11. customby dry flash chromatography
  12. washeluting with dichloromethane/methanol/0.880 NH3 (95:4.5:0.5)

Sources & evidence

ORD record
ord-3eabc0465efa4e10935ed01e6334ab7a
Source dataset
uspto-grants-2004_04
Patent number
US06723735B1

Reaction notes

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