1-Hydroxybenzotriazole → N-[2-[1-(tert-butoxycarbonyl)piperidin-4-yl]ethyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamide

HRID 1169390Notes

Reaction equation

HRID 1169390 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.ON1C2C=CC=CC=2N=N1.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][CH:42]([CH2:45][CH2:46][NH2:47])[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][CH:42]([CH2:45][CH2:46][NH:47][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])[CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 1514258tert-Butyl 4-(2-aminoethyl)piperidine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acid

Product 1

HCID 22989973N-[2-[1-(tert-butoxycarbonyl)piperidin-4-yl]ethyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamideYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxylic acid (1402 mg, 5.00 mmol) dissolved in DMF (30 ml) were added at 0° C. 1-hydroxybenzotriazole (743 mg, 5.50 mmol), 2-[1-(tert-butoxycarbonyl)piperidin-4-yl]ethylamine (1256 mg, 5.50 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1438 mg, 7.50 mmol), and the resulting mixture was stirred at room temperature for 8 hours. The reaction mixture was concentrated, ethyl acetate (120 ml) was added to the residue and the resulting mixture was washed successively with water (30 ml), an aqueous saturated solution of sodium bicarbonate (20 ml×3) and an aqueous saturated solution of sodium chloride (20 ml). The organic layer was dried with anhydrous magnesium sulfate and was then concentrated under reduced pressure, and the residue was subjected to column chromatography (silica gel, ethyl acetate/hexane=1/2→1/1). The objective fractions were concentrated under reduced pressure and were mixed with diisopropyl ether to collect an insoluble material by filtration. The insoluble material was washed with diisopropyl ether and was dried under reduced pressure to obtain N-[2-[1-(tert-butoxycarbonyl)piperidin-4-yl]ethyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamide (1.64 g, 3.34 mmol, 67%).

Workup

  1. additionwere added at 0° C
  2. concentrationThe reaction mixture was concentrated
  3. additionethyl acetate (120 ml) was added to the residue
  4. washthe resulting mixture was washed successively with water (30 ml)
  5. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  6. concentrationwas then concentrated under reduced pressure
  7. concentrationThe objective fractions were concentrated under reduced pressure
  8. additionwere mixed with diisopropyl ether
  9. customto collect an insoluble material
  10. filtrationby filtration
  11. washThe insoluble material was washed with diisopropyl ether
  12. customwas dried under reduced pressure

Sources & evidence

ORD record
ord-5fc504aaa2074891bcefdc69be70b4ca
Source dataset
uspto-grants-2003_09
Patent number
US06627651B1

Reaction notes

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