1-Hydroxybenzotriazole → HCID 17824062, compound

HRID 1169391Notes

Reaction equation

HRID 1169391 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.O[N:23]1C2C=CC=CC=2N=N1.C(OC(N1CCC(CN)CC1)=O)(C)(C)C.Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[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]([NH2:23])=[O:19])=[CH:13][C:12]=3[CH:21]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acid

Product 1

HCID 17824062HCID 17824062, compoundYield 172.5%

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), [1-(tert-butoxycarbonyl)piperidin-4-yl]methylamine (1393 mg, 6.50 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1438 mg, 7.50 mmol), and the resulting mixture was stirred at room temperature for 61 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate (100 ml) was added to the residue, and the resulting mixture was washed successively with water (10 ml×3), a 10% aqueous solution of potassium hydrogensulfate (10 ml×3), an aqueous saturated solution of sodium bicarbonate (10 ml×3) and an aqueous saturated solution of sodium chloride (10 ml). The organic layer was dried with anhydrous magnesium sulfate and then was concentrated under reduced pressure, and the residue was subjected to column chromatography (silica gel 80 g, ethyl acetate/hexane 1/2→1/1). The objective fractions were concentrated under reduced pressure to obtain N-[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamide (2409 mg).

Workup

  1. additionwere added at 0° C
  2. concentrationThe reaction mixture was concentrated under reduced pressure, ethyl acetate (100 ml)
  3. additionwas added to the residue
  4. washthe resulting mixture was washed successively with water (10 ml×3)
  5. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  6. concentrationwas concentrated under reduced pressure
  7. concentrationThe objective fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-5bb6c13798d44b4a9db60464333a43bb
Source dataset
uspto-grants-2003_09
Patent number
US06627651B1

Reaction notes

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