Triethylamine → Boc-Leu-Leu-Lys(Z)-OBzl

HRID 1513530Notes

Reaction equation

HRID 1513530 reaction equation
[NH2:1][C@H:2]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9].Cl.CCN(CC)CC.[NH:36]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[C@H:37]([C:42]([NH:44][C@H:45]([C:50](O)=[O:51])[CH2:46][CH:47]([CH3:49])[CH3:48])=[O:43])[CH2:38][CH:39]([CH3:41])[CH3:40].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.C(O)(=O)C>[NH:36]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[C@H:37]([C:42]([NH:44][C@H:45]([C:50]([NH:1][C@H:2]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:9])=[O:51])[CH2:46][CH:47]([CH3:48])[CH3:49])=[O:43])[CH2:38][CH:39]([CH3:41])[CH3:40]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7019882(S)-2-((S)-2-((tert-Butoxycarbonyl)amino)-4-methylpentanamido)-4-methylpentanoic acidHCID 11750132L-Lysine, N6-((phenylmethoxy)carbonyl)-, phenylmethyl ester, hydrochloride (1:1)

Product 1

HCID 12020549Boc-Leu-Leu-Lys(Z)-OBzlYield 93.6%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolvent3×

Procedure

A solution of H-Lys(Z)—OBzl.HCl (20.35 g, 50 mmol) in DMF (50.0 g) was treated with Et3N (5.26 g, 51 mmol) at 25 to 30° C. Boc-Leu-Leu-OH (17.57 g, 51 mmol) and HOBt (1.08 g, 8 mmol) were added followed by an additional portion of DMF (7.0 g). A solution of DCC (11.35 g, 55 mmol) in DMF (25.0 g) was added dropwise over a period of 30 min at 20° C. The reaction mixture was stirred for 4 h and the temperature was allowed to rise (to ca. 34° C.). Acetic acid (0.2 g) was added, the resulting suspension was filtered and the filter cake was rinsed with DMF (15.0 g). Acetone (126.0 g) was added to the filtrate, followed by two portions of H2O (66.5 g, 89.5 g-30 min apart). The resulting precipitate was filtered and the filter cake was washed with acetone (53.0 g) and H2O (212.0 g). The crude solid was triturated with a mixture of acetone (100 g) and H2O (400 g), filtered, washed with H2O and dried in vacuo at 40° C. to give Boc-Leu-Leu-Lys(Z)—OBzl (32.6 g, 93.4%).

Workup

  1. custom(to ca. 34° C.)
  2. filtrationthe resulting suspension was filtered
  3. washthe filter cake was rinsed with DMF (15.0 g)
  4. additionAcetone (126.0 g) was added to the filtrate
  5. filtrationThe resulting precipitate was filtered
  6. washthe filter cake was washed with acetone (53.0 g) and H2O (212.0 g)
  7. customThe crude solid was triturated with a mixture of acetone (100 g) and H2O (400 g)
  8. filtrationfiltered
  9. washwashed with H2O
  10. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-cf2584ec478c48229bb19d2aa2dfb6cd
Source dataset
uspto-grants-2012_07
Patent number
US08217142B2

Reaction notes

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