Triethylamine → N-t-butoxycarbonyl-L-alanylglycine iodopropargyl ester

HRID 1656155Notes

Reaction equation

HRID 1656155 reaction equation
FC(F)(F)C(O)=O.[I:8][CH:9]([O:12][C:13](=[O:16])[CH2:14][NH2:15])[C:10]#[CH:11].C(N(CC)CC)C.[C:24]([O:28][C:29]([NH:31][C@H:32]([C:34](O)=[O:35])[CH3:33])=[O:30])([CH3:27])([CH3:26])[CH3:25].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl>[I:8][CH:9]([O:12][C:13](=[O:16])[CH2:14][NH:15][C:34](=[O:35])[C@H:32]([CH3:33])[NH:31][C:29]([O:28][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:30])[C:10]#[CH:11]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 85082Tert-butoxycarbonylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86747289Glycine iodopropargyl ester trifluoroacetate2×

Product 1

HCID 86747290N-t-butoxycarbonyl-L-alanylglycine iodopropargyl esterYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a magnetically stirred, anhydrous dichloromethane (20 ml.) solution of glycine iodopropargyl ester trifluoroacetate (Compound #7) (2.00 g., 5.66 mmole) held at 0° C. with an ice-bath was added triethylamine (0.79 ml., 5.67 mmole), followed by N-t-butoxycarbonyl-L-alanine (1.07 g., 5.66 mmole), 1-hydroxybenzotriazole hydrate (0.77 g., 5.70 mmole) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.30 g., 6.78 mmole). The reaction mixture was held at 5° C. for 17 hours. The resultant solution was transferred to a separatory funnel and diluted to an approximate volume of 100 ml. with dichloromethane, then washed successively with water, 10% aqueous potassium hydrogen sulfate, water, saturated aqueous sodium bicarbonate, water and a final wash with saturated aqueous sodium chloride. The organic layer was dried with magnesium sulfate, filtered and concentrated in vacuo with a rotary evaporator to give 2.09 g. (90% yield) of the desired N-t-butoxycarbonyl-L-alanylglycine iodopropargyl ester as a dry white foam. 1H-NMR (200 MHz, CDCl3) δ=1.40, d, 3H; 1.47, 1.77, two s, 9H; 4.08, d, 2H; 4.24, m, 1H; 4.90, s, 2H; 5.06, d, 1H; 6.81, s, 1H. IR (CHCl3) 1160, 1375, 1495, 1690, 1755, 2200, 2985, 3440 cm-1.

Workup

  1. additiondiluted to an approximate volume of 100 ml
  2. washwith dichloromethane, then washed successively with water, 10% aqueous potassium hydrogen sulfate, water, saturated aqueous sodium bicarbonate, water
  3. washa final wash with saturated aqueous sodium chloride
  4. dry with materialThe organic layer was dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo with a rotary evaporator
  7. customto give 2.09 g

Sources & evidence

ORD record
ord-0740c66dc9ab4829bc1ab9080f610e81
Source dataset
uspto-grants-1993_10
Patent number
US05252745

Reaction notes

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