(+)-L-Leucine methyl ester → HCID 131731090, compound

HRID 1912376Notes

Reaction equation

HRID 1912376 reaction equation
[NH:1]([C:21]([O:23][CH2:24][CH:25]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]2[C:26]1=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[C@H:2]([C:18]([OH:20])=O)[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:6][CH:5]=1.[NH2:38][C@H:39]([C:44]([O:46][CH3:47])=[O:45])[CH2:40][CH:41]([CH3:43])[CH3:42].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.Cl.CC(C)=O>[NH:1]([C:21]([O:23][CH2:24][CH:25]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]2[C:26]1=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22])[C@H:2]([C:18]([NH:38][C@H:39]([C:44]([O:46][CH3:47])=[O:45])[CH2:40][CH:41]([CH3:43])[CH3:42])=[O:20])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 65105(+)-L-Leucine methyl esterHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27561174-((tert-Butoxycarbonyl)amino)-N-(((9H-fluoren-9-yl)methoxy)(hydroxy)methylidene)phenylalanine

Product 1

HCID 131731090HCID 131731090, compoundYield 70.3%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolvent2×HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

Fmoc-Phe(4-NHBoc)-OH (210 mg, 418 μmol, 1 equiv.) was dissolved in DCM and HCl.H-Leu-OMe (77 mg, 460 μmol, 1.1 equiv.), HBTU (190 mg, 502 μmol, 1.2 equiv.) and DiPEA (242 μl, 1.46 mmol, 3.5 equiv.) were added and the mixture stirred for 1 hour. after which it was washed with 1M HCl (2×), sat. aq. NaHCO3 (4×) and brine and dried over MgSO4. Column chromatography (10% acetone:PE->20% acetone:PE) yielded the title compound (206 mg, 294 μmol, 70%). 1H NMR (400 MHz, CDCl3): δ ppm 7.76 (d, J=7.5 Hz, 2H), 7.54 (t, J=6.9 Hz, 2H), 7.39 (t, J=7.4 Hz, 2H), 7.35-7.20 (m, 4H), 7.11 (d, J=7.1 Hz, 2H), 6.54 (s, 1H), 6.29 (d, J=6.6 Hz, 1H), 5.44 (d, J=7.2 Hz, 1H), 4.55 (td, J=8.4, 5.4 Hz, 1H), 4.41 (dd, J=10.3, 7.2 Hz, 1H), 4.32 (s, 1H), 4.18 (t, J=6.9 Hz, 1H), 3.68 (s, 3H), 3.15-2.94 (m, 2H), 1.65-1.39 (m, 3H), 1.51 (s, 9H), 0.97-0.78 (m, 6H). 13C NMR (101 MHz, CDCl3): δ ppm 172.74, 170.69, 155.89, 152.64, 143.67, 143.60, 141.16, 137.31, 130.58, 129.83, 127.64, 127.01, 124.98, 119.88, 118.55, 80.41, 67.11, 55.88, 52.17, 50.75, 46.95, 41.31, 37.78, 28.25, 24.63, 22.58, 21.81.

Workup

  1. washafter which it was washed with 1M HCl (2×), sat. aq. NaHCO3 (4×) and brine
  2. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-e5a406ac9df748afa2a896e1c3d1d731
Source dataset
uspto-grants-2013_12
Patent number
US08609610B2

Reaction notes

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