Benzaldehyde → HCID 70527317, compound

HRID 1156521Notes

Reaction equation

HRID 1156521 reaction equation
C[C:2]([CH2:12]C(O)C[OH:15])([CH3:11])[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH:17](=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=CC=1.[C:25]([OH:33])(=[O:32])[C:26]1C=CC=C[CH:27]=1.ClC1C=CC=[CH:37][N:36]=1.C[N:42]([CH:44]=[O:45])C>C1C=CC=CC=1>[C:44]([OH:45])(=[O:15])/[CH:27]=[CH:26]\[C:25]([OH:33])=[O:32].[CH3:12][C:2]([NH:36][CH2:37][CH:25]([OH:33])[CH2:26][O:24][C:17]1[CH:18]=[CH:23][CH:22]=[CH:21][N:42]=1)([CH3:11])[CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

7

Reactant 5

HCID 240BenzaldehydeHCID 243Benzoic AcidHCID 6228DimethylformamideHCID 79772-ChloropyridineHCID 20534797HCID 20534797, compound

Product 1

HCID 70527317HCID 70527317, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3.9 g. (16 mmole) 3-(1,1-dimethyl-3-phenylpropyl)-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 about 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), and 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/ether, and recrystallization of this from 2-propanol gave pure 2-[3-(1,1-dimethyl-3-phenylpropylamino)-2-hydroxy-1-propoxy]pyridine maleate; mp 144°-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. additionThe residue from about in 50 ml DMF 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
  13. temperature4 N HCl and the 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. dry with materialdried (Na2SO4)
  17. concentrationconcentrated
  18. customto give 3.0 g
  19. customto prepare
  20. customthe maleate salt in 2-propanol/ether, and recrystallization of this from 2-propanol

Sources & evidence

ORD record
ord-d4aa13128b294d2ab6cb2a07d51adf13
Source dataset
uspto-grants-1982_06
Patent number
US04336261

Reaction notes

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