Triethylamine → methyl (S)-3-(4-but-2-ynyloxybenzoylamino)-2-cyclohexylpropanoate

HRID 1777271Notes

Reaction equation

HRID 1777271 reaction equation
ON1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH2:23]([O:27][C:28]1[CH:36]=[CH:35][C:31]([C:32]([OH:34])=O)=[CH:30][CH:29]=1)[C:24]#[C:25][CH3:26].Cl.Cl.[NH2:39][CH2:40][C@H:41](N1CCCCC1)[C:42]([O:44][CH3:45])=[O:43].C(N(CC)CC)C>CN(C)C=O>[CH2:23]([O:27][C:28]1[CH:29]=[CH:30][C:31]([C:32]([NH:39][CH2:40][C@H:41]([CH:5]2[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]2)[C:42]([O:44][CH3:45])=[O:43])=[O:34])=[CH:35][CH:36]=1)[C:24]#[C:25][CH3:26]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 222825564-But-2-ynyloxy-benzoic acidHCID 67494635methyl (S)-3-amino-2-piperidin-1-ylpropanoate dihydrochloride

Product 1

HCID 67056389methyl (S)-3-(4-but-2-ynyloxybenzoylamino)-2-cyclohexylpropanoateYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

420 mg (3.1 mmol) of 1-hydroxybenzotriazole and 600 mg (3.1 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride are added to a solution of 540 mg (3.1 mmol) of 4-but-2-ynyloxybenzoic acid in 10 ml of dimethylformamide. The reaction medium is stirred for 15 min at ambient temperature then 630 mg (2.8 mmol) of methyl (S)-3-amino-2-piperidin-1-yl-propanoate dihydrochloride in 10 ml of dimethylformamide and 0.8 ml (5.7 mmol) of triethylamine are added. The reaction medium is stirred at ambient temperature for 18 h. The organic phase is washed with an aqueous solution of sodium hydrogen carbonate 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 99/1 dichloromethane/methanol mixture. 580 mg (58%) of methyl (S)-3-(4-but-2-ynyloxybenzoylamino)-2-cyclohexylpropanoate are obtained in the form of a colourless oil.

Workup

  1. stirringThe reaction medium is stirred at ambient temperature for 18 h
  2. washThe organic phase is washed with an aqueous solution of sodium hydrogen carbonate
  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 99/1 dichloromethane/methanol mixture

Sources & evidence

ORD record
ord-714ddae8c8644396931c40f533bc8b28
Source dataset
uspto-grants-2016_02
Patent number
US09266848B2

Reaction notes

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