Triethylamine → Dimethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-2-[(4-but-2-ynyloxybenzoylamino)methyl]malonate

HRID 517489Notes

Reaction equation

HRID 517489 reaction equation
C(N(CC)CC)C.[CH2:8]([O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=[O:18])=[CH:15][CH:14]=1)[C:9]#[C:10][CH3:11].[NH2:22][CH2:23][C:24]([N:33]1[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]1)([C:29]([O:31][CH3:32])=[O:30])[C:25]([O:27][CH3:28])=[O:26]>O1CCCC1>[C:42]([O:41][C:39]([N:36]1[CH2:37][CH2:38][N:33]([C:24]([CH2:23][NH:22][C:17](=[O:18])[C:16]2[CH:20]=[CH:21][C:13]([O:12][CH2:8][C:9]#[C:10][CH3:11])=[CH:14][CH:15]=2)([C:29]([O:31][CH3:32])=[O:30])[C:25]([O:27][CH3:28])=[O:26])[CH2:34][CH2:35]1)=[O:40])([CH3:44])([CH3:45])[CH3:43]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 57848700Dimethyl 2-aminomethyl-2-(4-tert-butoxycarbonylpiperazin-1-yl)malonateHCID 593240144-But-2-ynyloxybenzoyl chloride

Product 1

HCID 67056950Dimethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-2-[(4-but-2-ynyloxybenzoylamino)methyl]malonateYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2 ml (14.2 mmol) of triethylamine then 2.9 g (14.2 mmol) of 4-but-2-ynyloxybenzoyl chloride diluted in 30 ml of tetrahydrofuran are added to a solution of 4 g (11.6 mmol) of dimethyl 2-aminomethyl-2-(4-tert-butoxycarbonylpiperazin-1-yl)malonate (prepared as described in example 1-3) in 40 ml of tetrahydrofuran. The reaction medium is stirred at ambient temperature for 1 h, then hydrolysed and the product is extracted with ethyl acetate. The organic phase is washed with water then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated. The crude product obtained is purified by chromatography over silica gel eluted with a 5/5 heptane/ethyl acetate mixture. 4.2 g (70%) of dimethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-2-[(4-but-2-ynyloxybenzoylamino)methyl]malonate are obtained in the form of a beige solid.

Workup

  1. extractionhydrolysed and the product is extracted with ethyl acetate
  2. washThe organic phase is washed with water
  3. dry with materialwith a saturated aqueous solution of sodium chloride, dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product obtained
  7. customis purified by chromatography over silica gel
  8. washeluted with a 5/5 heptane/ethyl acetate mixture

Sources & evidence

ORD record
ord-b84be03d09a74bacbaad626738b49e0a
Source dataset
uspto-grants-2015_08
Patent number
US09115102B2

Reaction notes

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