1-Hydroxybenzotriazole hydrate → 1-t-Butoxycarbonyl-4-{1-(4-fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-4-hydroxypiperidine

HRID 497341Notes

Reaction equation

HRID 497341 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH:15]([C:23]([OH:25])=O)[C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[C:28]1([CH2:38][CH2:39][CH2:40][CH2:41][N:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][CH:29]=1.Cl.CNC(NC)CCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.C(OCC)(=O)C.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH:15]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[C:23]([N:45]2[CH2:44][CH2:43][N:42]([CH2:41][CH2:40][CH2:39][CH2:38][C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30][CH:29]=3)[CH2:47][CH2:46]2)=[O:25])([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 4

HCID 27960291-Hydroxybenzotriazole hydrateHCID 223186301-t-Butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]-4-hydroxypiperidineHCID 223186681-(4-Naphthalen-1-yl-butyl)piperazine dihydrochlorideHCID 574299851-(3,3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

Product 1

HCID 178506631-t-Butoxycarbonyl-4-{1-(4-fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-4-hydroxypiperidineYield 48.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

2.37 g of 1-t-Butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]-4-hydroxypiperidine obtained in Example 11(1) was dissolved in 20 ml of dimethylformamide, and 2.50 g of 1-(4-naphthalen-1-yl-butyl)piperazine dihydrochloride, 1.9 g of 1-(3,3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 1.9 g of 1-hydroxybenzotriazole monohydrate and 3.5 ml of triethylamine were added, followed by stirring at room temperature overnight. The reaction solution was diluted with ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (Chromatorex NH, hexane:ethyl acetate=3:1) to give 1.96 g of 1-t-butoxycarbonyl-4-{1-(4-fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-4-hydroxypiperidine as an oil.

Workup

  1. washwashed with a saturated aqueous sodium bicarbonate solution
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. customAfter removal of the drying agent
  4. filtrationby filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by a silica gel column chromatography (Chromatorex NH, hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-ebe263fc27064fd0b0b0890c1492f265
Source dataset
uspto-grants-2005_09
Patent number
US06949552B2

Reaction notes

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