Dicyclohexylcarbodiimide → Boc-valine norvaline leucinamide

HRID 399102Notes

Reaction equation

HRID 399102 reaction equation
[C:1]([NH:8][C@H:9]([C:13]([OH:15])=[O:14])[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH2:16][C@H:17]([C:21]([OH:23])=[O:22])[CH2:18][CH2:19][CH3:20].[NH2:24][C@H:25]([C:30]([NH2:32])=[O:31])[CH2:26][CH:27]([CH3:29])[CH3:28].C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([NH:8][C@H:9]([C:13]([OH:15])=[O:14])[CH:10]([CH3:11])[CH3:12])([O:3][C:4]([CH3:6])([CH3:5])[CH3:7])=[O:2].[NH2:16][C@H:17]([C:21]([OH:23])=[O:22])[CH2:18][CH2:19][CH3:20].[NH2:24][C@H:25]([C:30]([NH2:32])=[O:31])[CH2:26][CH:27]([CH3:29])[CH3:28]

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 18665785Norvaline leucinamide

Product 1

HCID 18665773Boc-valine norvaline leucinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Boc-norvaline (2.0 g, 9.2 mmol) and leucinamide (1.53 g, 9.2 mmol) were dissolved in dry DMF (90 mL). The reaction was cooled to 0° C. and DCC (2.3 g, 11 mmol), HOBt (1.48 g, 11 mmol), and DEA (1.9 mL, 11 mmol) added. The mixture was stirred for 20 min at 0° C. and allowed to slowly warm to room temperature overnight (17 h). The mixture was concentrated to 1/3 its original volume, cooled, and filtered. The filtrate was concentrated, affording a yellow oil which was purified by column chromatography (SiO2, 1:1 hexanes/EtOAc→EtOAc) providing Boc-norvaline-leucinamide as white solid (selected signals 400 MHz, 1H NMR, CDCI3: δ 4.93 (m, 1 H), 4.45 (m, 1 H), 3.99 (m, 1 H), 1.81-1.71 (m, 2 H), 1.68-1.50 (m, 4 H), 1.41 (s, 9 H), 1.4-1.3 (m, 2 H), 0.9 (m, 9 H)). The Boc-protecting group was removed by treatment of Boc-norvaline-leucinamide (1.5 g, 4.6 mmol) with 50% TFA/DCM (60 mL) at room temperature (30 min). The reaction mixture was concentrated in vacuo and the peptide triturated with diethyl ether and dried in vacuo overnight providing norvaline-leucinamide as a foamy white solid (Electrospray MS M+H=230.1). Boc-valine (233 mg, 1.1 mmol) and norvaline-leucinamide (246 mg, 1.1 mmol) were dissolved in DMF (5 mL) and the solution cooled to 0° C. DCC (266 mg, 1.3 mmol), HOBt (174 mg, 1.3 mmol), and DIEA (224 μL, 1.3 mmol) were added and the reaction allowed to slowly warm to RT (overnight, 17 h). The reaction was filtered and the filtrate concentrated in vacuo affording a solid which was purified by column chromatography (SiO2, EtOAc). This provided the desired Boc-valine-norvaline-leucinamide as a white solid.

Workup

  1. temperatureto slowly warm to RT (overnight, 17 h)
  2. filtrationThe reaction was filtered
  3. concentrationthe filtrate concentrated in vacuo
  4. customaffording a solid which
  5. customwas purified by column chromatography (SiO2, EtOAc)

Sources & evidence

ORD record
ord-24fd644573784b5f96b3c7b3c6df4ec6
Source dataset
uspto-grants-1998_10
Patent number
US05817757

Reaction notes

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