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

HRID 1169392Notes

Reaction equation

HRID 1169392 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][CH2:47][NH2:48])[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][CH2:47][NH:48][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 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 105646997-(4-Methylphenyl)-2,3-dihydrobenzooxepine-4-carboxylic acidHCID 22990164tert-Butyl 4-(3-aminopropyl)piperidine-1-carboxylate

Product 1

HCID 22989950N-[3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamideYield 99%

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), 3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propylamine (1333 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 18 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 (10×3 ml), 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 was then concentrated under reduced pressure, and the residue was subjected to column chromatography (silica gel 80g, ethyl acetate/hexane=1/3→1/1)]. The objective fractions were concentrated under reduced pressure to obtain N-[3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propyl]-7-(4-methylphenyl)-2,3-dihydro-1-benzooxepine-4-carboxamide (2498 mg, 4.95 mmol, 99%).

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 (10×3 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

Sources & evidence

ORD record
ord-2e5eafcb179e475396f629ae3375d2c7
Source dataset
uspto-grants-2003_09
Patent number
US06627651B1

Reaction notes

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