Benzaldehyde → HCID 70527317, compound

HRID 1156522Notes

Reaction equation

HRID 1156522 reaction equation
[CH3:1][C:2]([NH:12][CH2:13][CH:14]([OH:17])[CH2:15][OH:16])([CH3:11])[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(=[O:25])C1C=CC=CC=1.[C:26]([OH:34])(=[O:33])C1C=CC=CC=1.Cl[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1>CC(O)C.CN(C=O)C.C1C=CC=CC=1>[C:15]([OH:16])(=[O:25])/[CH:14]=[CH:13]\[C:26]([OH:34])=[O:33].[CH3:11][C:2]([NH:12][CH2:13][CH:14]([OH:17])[CH2:15][O:16][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1)([CH3:1])[CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

8

Reactant 4

HCID 240BenzaldehydeHCID 243Benzoic AcidHCID 79772-ChloropyridineHCID 12855751HCID 12855751, compound

Product 1

HCID 70527317HCID 70527317, compound

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 3776IsopropanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3.9 g. (16 mmole) 3-(1,1-dimethyl-3-phenylpropylamino)-1,2-dihydroxypropane, 15 ml. benzaldehyde, 9 ml. benzene, and 100 mg. benzoic acid was refluxed for 16 hours while a Dean-Stark trap was being used to collect the water. The solution was diluted with benzene and washed with aqueous potassium carbonate. The mixture was concentrated and the residue was distilled under reduced pressure (0.4 mm.) at a pot temperature of 75°-80° C. The residue from above in 50 ml. DMF was then added dropwise to sodium hydride (1.0 g. of a 50% oil dispersion washed with hexane) in 25 ml. DMF. After the addition, stirring was continued for 1 hour. 2-Chloropyridine (1.80 g., 16 mmole) in 25 ml. DMF was added and the mixture heated at 70° C. for 16 hours. Most of the DMF was evaporated. Water and ether were added and the layers separated. The ether solution was washed twice with 100 ml 4 N HCl and the combined acid washings were heated on a steam bath for 1/2 hour. After washing with ether, the aqueous phase was made basic with KOH. The oil was extracted with CH2Cl2, dried (NA2SO4), anc concentrated to give 3.0 g. (60%) of the crude free base. A small sample was used to prepare the maleate salt in 2-propanol gave pure 2-[3-(1,1-dimethyl-3-phenylpropylamino)-2-hydroxy-1-propoxy]pyridine maleate, mp 141°-146° C.

Workup

  1. customto collect the water
  2. additionThe solution was diluted with benzene
  3. washwashed with aqueous potassium carbonate
  4. concentrationThe mixture was concentrated
  5. distillationthe residue was distilled under reduced pressure (0.4 mm.) at a pot temperature of 75°-80° C
  6. additionDMF was then added dropwise to sodium hydride (1.0 g
  7. washof a 50% oil dispersion washed with hexane) in 25 ml
  8. additionAfter the addition
  9. customMost of the DMF was evaporated
  10. additionWater and ether were added
  11. customthe layers separated
  12. washThe ether solution was washed twice with 100 ml 4 N HCl
  13. temperaturethe combined acid washings were heated on a steam bath for 1/2 hour
  14. washAfter washing with ether
  15. extractionThe oil was extracted with CH2Cl2
  16. customdried (NA2SO4), anc
  17. concentrationconcentrated
  18. customto give 3.0 g

Sources & evidence

ORD record
ord-cbf8a271a7234b908db276fe594ede02
Source dataset
uspto-grants-1982_06
Patent number
US04336261

Reaction notes

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