Pyridine → N-(3-acetyl-2-hydroxyphenyl)-2-(benzyloxymethyl)chromane-6-carboxamide

HRID 1603876Notes

Reaction equation

HRID 1603876 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]1[CH2:19][CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:20]([OH:22])=O)[CH:16]=2)[O:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][C:24]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([NH2:32])[C:27]=1[OH:33])=[O:25].N1C=CC=CC=1>C(Cl)(=O)C(Cl)=O.C(Cl)Cl>[C:24]([C:26]1[C:27]([OH:33])=[C:28]([NH:32][C:20]([C:15]2[CH:16]=[C:17]3[C:12](=[CH:13][CH:14]=2)[O:11][CH:10]([CH2:9][O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:19][CH2:18]3)=[O:22])[CH:29]=[CH:30][CH:31]=1)(=[O:25])[CH3:23]

Participants

6

Reactant 3

HCID 1049PyridineHCID 4592943-Amino-2-hydroxyacetophenoneHCID 196062512-(Benzyloxymethyl)-6-chromanecarboxylic acid

Product 1

HCID 19606371N-(3-acetyl-2-hydroxyphenyl)-2-(benzyloxymethyl)chromane-6-carboxamideYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 65578Oxalyl chlorideSolvent

Conditions

Temperature
75 °C

Procedure

A suspension of 2-(benzyloxymethyl)-6-chromanecarboxylic acid (0.700 g, 2.35 mmol) in oxalyl chloride (5.98 ml) was heated at 75° C. for 35 minutes. The oxalyl chloride excess was evaporated off in a nitrogen stream and the resulting residue was dissolved in the minimum amount of dry methylene chloride. This solution was added at 0° C. and under inert atmosphere to a solution of 3-amino-2-hydroxyacetophenone (0.550 g, 2.37 mmol), pyridine (7 ml) and dry methylene chloride (40 ml). The resulting mixture was left under stirring at room temperature for 18 h, then diluted with methylene chloride (40 ml), washed successively with 1M HCl and a sodium chloride saturated solution, dried and the solvent was evaporated off under reduced pressure. A crude was obtained which was purified by chromatography through a silica gel column, eluting with petroleum ether:chloroform mixtures of increasing polarity. At a 40% chloroform proportion, 0.732 g of the title compound were eluted (72% yield).

Workup

  1. customThe oxalyl chloride excess was evaporated off in a nitrogen stream
  2. dissolutionthe resulting residue was dissolved in the minimum amount of dry methylene chloride
  3. waitThe resulting mixture was left
  4. washwashed successively with 1M HCl
  5. dry with materiala sodium chloride saturated solution, dried
  6. customthe solvent was evaporated off under reduced pressure
  7. customA crude was obtained which
  8. customwas purified by chromatography through a silica gel column
  9. washeluting with petroleum ether
  10. temperaturechloroform mixtures of increasing polarity
  11. washAt a 40% chloroform proportion, 0.732 g of the title compound were eluted (72% yield)

Sources & evidence

ORD record
ord-6d527203f6da4a4388f018c06a845114
Source dataset
uspto-grants-1999_11
Patent number
US05990142

Reaction notes

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