Triethylamine → 4-Hydroxymethyl-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine

HRID 1169374Notes

Reaction equation

HRID 1169374 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[O:17][CH2:16][CH2:15][C:14]([C:18](O)=[O:19])=[CH:13][C:12]=3[CH:21]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC)=O>C1COCC1>[OH:19][CH2:18][C:14]1[CH2:15][CH2:16][O:17][C:11]2[CH:10]=[CH:9][C:8]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=3)=[CH:21][C:12]=2[CH:13]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acid

Product 1

HCID 229901384-Hydroxymethyl-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepineYield 88.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

Into a solution of 7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxylic acid (841 mg) and triethylamine (0.42 ml) in THF (15 ml) was added dropwise at −5° C. a solution of ethyl chloroformate (0.29 ml)/THF (2 ml). The resulting mixture was stirred at −5° C. for 30 minutes, and an insoluble material was removed by filtration. Into the filtrate was added dropwise under ice cooling a solution of sodium borohydride (284 mg)/water (6 ml). After stirring at room temperature for 1.5 hours, the reaction mixture was mixed with 1 N hydrochloric acid and was extracted with ethyl acetate. The extract was washed successively with water, a 1 N aqueous solution of sodium hydroxide, water and an aqueous solution of sodium chloride, was dried (anhydrous magnesium sulfate) and was then concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/diethyl ether/hexane to obtain 4-hydroxymethyl-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine (708 mg) as colorless crystals.

Workup

  1. customan insoluble material was removed by filtration
  2. additionInto the filtrate was added dropwise under ice cooling a solution of sodium borohydride (284 mg)/water (6 ml)
  3. stirringAfter stirring at room temperature for 1.5 hours
  4. additionthe reaction mixture was mixed with 1 N hydrochloric acid
  5. extractionwas extracted with ethyl acetate
  6. washThe extract was washed successively with water
  7. dry with materiala 1 N aqueous solution of sodium hydroxide, water and an aqueous solution of sodium chloride, was dried (anhydrous magnesium sulfate)
  8. concentrationwas then concentrated under reduced pressure
  9. customThe residue was recrystallized from ethyl acetate/diethyl ether/hexane

Sources & evidence

ORD record
ord-4c7dac58bf1a41e69791366ab1a2735b
Source dataset
uspto-grants-2003_09
Patent number
US06627651B1

Reaction notes

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