Phosphorus oxide (P4O10) → beta-[(5-Hydroxypentyl)amino]-4-methoxy-alpha-(4-methoxyphenyl)benzeneethanol fumarate hemihydrate

HRID 1381522Notes

Reaction equation

HRID 1381522 reaction equation
[C:1]1([C:9]([CH:11]([C:13]2[CH:20]=[CH:19][C:16]([O:17][CH3:18])=[CH:15][CH:14]=2)[OH:12])=O)[CH:8]=[CH:7][C:4]([O:5][CH3:6])=[CH:3][CH:2]=1.[NH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][OH:27].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[BH4-].[Na+].[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]/[C:47]([OH:49])=[O:48]>C(O)C>[OH2:5].[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]/[C:47]([OH:49])=[O:48].[OH:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][NH:21][CH:9]([C:1]1[CH:8]=[CH:7][C:4]([O:5][CH3:6])=[CH:3][CH:2]=1)[CH:11]([C:13]1[CH:20]=[CH:19][C:16]([O:17][CH3:18])=[CH:15][CH:14]=1)[OH:12].[OH:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][NH:21][CH:9]([C:1]1[CH:8]=[CH:7][C:4]([O:5][CH3:6])=[CH:3][CH:2]=1)[CH:11]([C:13]1[CH:20]=[CH:19][C:16]([O:17][CH3:18])=[CH:15][CH:14]=1)[OH:12].[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]/[C:47]([OH:49])=[O:48]

Participants

7

Reactant 5

HCID 14812Phosphorus oxide (P4O10)HCID 756345-Aminopentan-1-olHCID 954154,4'-DimethoxybenzoinHCID 444972Fumaric AcidHCID 4311764Sodium borohydride

Product 1

HCID 131715855beta-[(5-Hydroxypentyl)amino]-4-methoxy-alpha-(4-methoxyphenyl)benzeneethanol fumarate hemihydrateYield 59.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of anisoin (10.0 g, 0.037 mole), 5-amino-1-pentanol (11.37 g, 0.11 mole) and phosphorus pentoxide (2.5 g, 0.018 mole) was heated for 4 hours in an oil bath at 105° C. with a nitrogen purge. Water was produced and evaporated as the reaction proceeded to completion. The reaction mixture was cooled and chloroform (100 ml) added. The chloroform layer was washed with dilute acid (100 ml×2). The aqueous washes were combined, made basic and washed with chloroform. The organic layer was concentrated and dissolved in 100 ml of ethanol, to which solution an aqueous solution of sodium borohydride (0.074 mole) was added. The resulting mixture was stirred for 1.5 hr and concentrated to dryness. The residue was partitioned between 100 ml of 25% sodium hydroxide and 500 ml of methylene chloride. The methylene chloride layer was washed with water (2×100 ml), concentrated and the concentrate was dissolved in methyl isobutylketone. Fumaric acid (0.037 mole) was added. The precipitate was recrystallized in acetone, filtered off and dried to give 7.09 g (52.9%) of crystals, m.p. 172°-175° C.

Workup

  1. custompurge
  2. customWater was produced
  3. customevaporated as the reaction
  4. temperatureThe reaction mixture was cooled
  5. additionchloroform (100 ml) added
  6. washThe chloroform layer was washed
  7. additionwith dilute acid (100 ml×2)
  8. washwashed with chloroform
  9. concentrationThe organic layer was concentrated
  10. additionwas added
  11. concentrationconcentrated to dryness
  12. customThe residue was partitioned between 100 ml of 25% sodium hydroxide and 500 ml of methylene chloride
  13. washThe methylene chloride layer was washed with water (2×100 ml)
  14. concentrationconcentrated
  15. dissolutionthe concentrate was dissolved in methyl isobutylketone
  16. customThe precipitate was recrystallized in acetone
  17. filtrationfiltered off
  18. customdried

Sources & evidence

ORD record
ord-6d567284397f4e579da6aeaa10df41a0
Source dataset
uspto-grants-1989_02
Patent number
US04803200

Reaction notes

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