Hydrochloric Acid → N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide

HRID 1870516Notes

Reaction equation

HRID 1870516 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(Cl)(=O)C(Cl)=O.[Si]([O:35][CH2:36][C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=1)(C(C)(C)C)(C)C.C(N(CC)CC)C.Cl.C(=O)([O-])O.[Na+].C(OC(C)C)(C)C>O1CCCC1.CN(C)C=O.CC(C)=O.C(OCC)(=O)C.O>[OH:35][CH2:36][C:37]1[CH:38]=[CH:39][C:40]([NH:41][C:18]([C:14]2[CH2:15][CH2:16][O:17][C:11]3[CH:10]=[CH:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=4)=[CH:21][C:12]=3[CH:13]=2)=[O:19])=[CH:42][CH:43]=1

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 7914Diisopropyl EtherHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acidHCID 110754704-Aminobenzyloxy-tert-butyldimethylsilane

Product 1

HCID 18472380N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamideYield 107.5%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 180AcetoneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylic acid (0.6 g, 2.1 mmol) in tetrahydrofuran (10 ml) were added oxalyl chloride (0.33 ml, 4.3 mmol) and N,N-dimethylformamide (1 drop) at 0° C., and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated, and the residue was dissolved in tetrahydrofuran (6 ml). To the mixture was dropwise added 4-(t-butyldimethylsilyloxymethyl)aniline (0.56 g, 2.4 mmol) and triethylamine (0.36 ml, 2.6 mmol) in tetrahydrofuran (2 ml) at 0° C., and the mixture was stirred at room temperature for 16 hours. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution and dried with magnesium sulfate. The solvent was evaporated, and the residue was subjected to silica gel column chromatography. Crude amide (1.1 g) was obtained from fractions of hexane:ethyl acetate=5:1. This product was dissolved in acetone (8 ml), and to the mixture was dropwise added 6N hydrochloric acid. The mixture was stirred for 1 hour. To the mixture were added 1% sodium hydrogen carbonate (100 ml) and diisopropylether (100 ml), and precipitate was filtered, which were dissolved in acetone. The mixture was dried with magnesium sulfate, and the solvent was evaporated. The resulting powder was recrystallized from acetone-diisopropyl-ether to give N-(4-hydroxymethylphenyl)-7-(4-methylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (0.87 g) as colorless crystals.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in tetrahydrofuran (6 ml)
  3. customat 0° C.
  4. stirringthe mixture was stirred at room temperature for 16 hours
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed with saturated sodium chloride solution
  7. dry with materialdried with magnesium sulfate
  8. customThe solvent was evaporated
  9. customCrude amide (1.1 g) was obtained from fractions of hexane
  10. stirringThe mixture was stirred for 1 hour
  11. filtrationwas filtered
  12. dissolutionwhich were dissolved in acetone
  13. dry with materialThe mixture was dried with magnesium sulfate
  14. customthe solvent was evaporated
  15. customThe resulting powder was recrystallized from acetone-diisopropyl-ether

Sources & evidence

ORD record
ord-96a3577b3d274f27a59e369d841bbac1
Source dataset
uspto-grants-2000_08
Patent number
US06096780

Reaction notes

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