Triethylamine → 1-N-[N-(tert-butoxycarbonyl)-3-(thiazol-4-yl)-L-alanyl]-(2R)-2-methylpyrrohdine

HRID 655982Notes

Reaction equation

HRID 655982 reaction equation
ON1[C:6]2[CH:7]=[CH:8][CH:9]=C[C:5]=2[N:4]=N1.C(N(CC)CC)C.[C:18]([O:22][C:23]([NH:25][C@H:26]([C:33]([OH:35])=O)[CH2:27][C:28]1[N:29]=[CH:30][S:31][CH:32]=1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>O1CCCC1>[C:18]([O:22][C:23]([NH:25][C@H:26]([C:33]([N:4]1[CH2:5][CH2:6][CH2:7][C@H:8]1[CH3:9])=[O:35])[CH2:27][C:28]1[N:29]=[CH:30][S:31][CH:32]=1)=[O:24])([CH3:19])([CH3:20])[CH3:21]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2734486(S)-2-((tert-Butoxycarbonyl)amino)-3-(thiazol-4-yl)propanoic acid

Product 1

HCID 866181281-N-[N-(tert-butoxycarbonyl)-3-(thiazol-4-yl)-L-alanyl]-(2R)-2-methylpyrrohdineYield 323.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N,N-dicyclohexylcarbodiimide (10.83 g, 52.5 mmol), N-hydroxybenzotriazole (2.03 g, 15 mmol) and triethylamine (7.7 ml, 55.2 mmol) were added to a solution (130 ml) of N-(tert-butoxycarbonyl)-3-(thiazol-4-yl)-L-alanine (1) (13.62 g, 50 mmol) obtained by the method described in literatures (J. Am. Chem. Soc. 73, 2935 (1951) and Chem. Pharm. Bull. 38, 103 (1950)) and 2(R)-2-methylpyrrolidine p-toluenesulfonic acid (2) (12.79 g, 50 mmol) obtained by the method described in a literature (Helv. Chim. Acta, 34, 2202 (1951)) in tetrahydrofuran. The mixture was stirred for 20 hours at room temperature. After the precipitates are filtered off, the obtained filtrate was concentrated under reduced pressure. Thus-obtained residue was dissolved in ethyl acetate (200 ml) and the solution were washed with an aqueous solution of sodium hydrogencarbonate and water, successively. The organic layers were dried over magnesium sulfate and concentrated under reduced pressure to give a title compound (3) (16.45 g, 100%) as oil.

Workup

  1. customobtained by the method
  2. customobtained by the method
  3. filtrationAfter the precipitates are filtered off
  4. concentrationthe obtained filtrate was concentrated under reduced pressure
  5. dissolutionThus-obtained residue was dissolved in ethyl acetate (200 ml)
  6. washthe solution were washed with an aqueous solution of sodium hydrogencarbonate and water
  7. dry with materialThe organic layers were dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4c2ae316c8444c1d83cd01577cd4263a
Source dataset
uspto-grants-2011_12
Patent number
US08071633B2

Reaction notes

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