Acetic Acid → Racemic tert-butyl 2-(3,4-dichlorophenyl)-6-methoxy-4-oxochroman-3-carboxylate

HRID 409522

Reaction equation

HRID 409522 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10](=[O:19])[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[Cl:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH:24]=O.N1CCCCC1.C(O)(=O)C>C(O)(C)C.O>[Cl:20][C:21]1[CH:22]=[C:23]([CH:24]2[CH:11]([C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])[C:10](=[O:19])[C:3]3[C:2](=[CH:7][CH:6]=[C:5]([O:8][CH3:9])[CH:4]=3)[O:1]2)[CH:26]=[CH:27][C:28]=1[Cl:29]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8082PiperidineHCID 227103,4-DichlorobenzaldehydeHCID 67155884Tert-butyl 3-(2-hydroxy-5-methoxyphenyl)-3-oxopropanoate

Product 1

HCID 67156193Racemic tert-butyl 2-(3,4-dichlorophenyl)-6-methoxy-4-oxochroman-3-carboxylateYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

A solution of tert-butyl 3-(2-hydroxy-5-methoxyphenyl)-3-oxopropanoate (500 mg, 1.88 mmol) in isopropanol (5.0 mL) was treated with 3,4-dichlorobenzaldehyde (329 mg, 1.88 mmol), piperidine (20 μL, 188 μmol) and acetic acid (10 μL, 188 μmol). The reaction mixture was heated at reflux overnight, and then treated with water (1.0 mL). The resulting mixture was cooled to rt and then concentrated under vacuum to yield a residue. The residue was purified by column chromatography (silica gel, 2-25% ethyl acetate-hexane) to provide racemic tert-butyl 2-(3,4-dichlorophenyl)-6-methoxy-4-oxochroman-3-carboxylate as a yellow oil (380 mg, 48%). This material was used without further purification in Step 3 below.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. concentrationconcentrated under vacuum
  4. customto yield a residue
  5. customThe residue was purified by column chromatography (silica gel, 2-25% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-cd93dc974e8f437fa39820e2702690eb
Source dataset
uspto-grants-2014_06
Patent number
US08759390B2

Linked notes

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