Diisopropylethylamine → Boc-proline (p-cyanobenzyl)amide

HRID 1459004Notes

Reaction equation

HRID 1459004 reaction equation
[N:1]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH2:14][CH2:13][C@H:2]1[C:3]([O:5]N1C(=O)CCC1=O)=O.Cl.[C:24]([C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH2:31])=[CH:28][CH:27]=1)#[N:25].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:24]([C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH:31][C:3](=[O:5])[C@@H:2]2[CH2:13][CH2:14][CH2:15][N:1]2[C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])=[CH:28][CH:27]=1)#[N:25]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 8538831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) 2-(2,5-dioxo-1-pyrrolidinyl) ester, (2S)-HCID 99422504-(Aminomethyl)benzonitrile hydrochloride

Product 1

HCID 54165357Boc-proline (p-cyanobenzyl)amideYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

276 g of Boc-Pro-OSu (0.88 mol) were introduced into 2 l of methylene chloride at 0° C. To this solution were added successively 163.9 g of 4-cyanobenzylamine hydrochloride (0.97 mol) and 230 ml of diisopropylethylamine (1.34 mol). The suspension was stirred in a melting ice bath for 48 h and then filtered. The filtrate was extracted with 20% strength NaHSO4 solution (4×), saturated NaHCO3 solution (3×) and saturated sodium chloride solution (2×), dried and evaporated in a rotary evaporator. Recrystallization of the residue from methyl tert-butyl ether resulted in isolation of 261 g (90%) of white crystals, m.p. 124°-125° C.

Workup

  1. filtrationfiltered
  2. extractionThe filtrate was extracted with 20% strength NaHSO4 solution (4×), saturated NaHCO3 solution (3×) and saturated sodium chloride solution (2×)
  3. customdried
  4. customevaporated in a rotary evaporator
  5. customRecrystallization of the residue from methyl tert-butyl ether

Sources & evidence

ORD record
ord-2e7565560f154669a2b78faec9ac2b83
Source dataset
uspto-grants-1998_12
Patent number
US05852051

Reaction notes

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