Diisopropylethylamine → N-Fmoc-glycyl-L-phenylalanyl-glycine

HRID 39264

Reaction equation

HRID 39264 reaction equation
[C:1]([NH:18][CH2:19][C:20](O)=[O:21])([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:56][C@H:57]([C:65]([NH:67][CH2:68][C:69]([OH:71])=[O:70])=[O:66])[CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1>CN(C=O)C.C(OCC)(=O)C>[CH:7]1[C:6]2[CH:5]([CH2:4][O:3][C:1]([NH:18][CH2:19][C:20]([NH:56][C@H:57]([C:65]([NH:67][CH2:68][C:69]([OH:71])=[O:70])=[O:66])[CH2:58][C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=3)=[O:21])=[O:2])[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]=2[CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 93124Fmoc-Gly-OHHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 6992304Phe-Gly

Product 1

HCID 15222489N-Fmoc-glycyl-L-phenylalanyl-glycine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Fmoc-glycine (297 mg, 1.00 mmol) in DMF (5 mL) at 0° C. was added DIEA (348 μL, 2.00 mmol) and HBTU (379 mg, 1.00 mmol). After stirring for 10 min at 0° C., the resulting activated ester solution was added to crude dipeptide 73 (1.00 mmol) and the reaction mixture was stirred for 2 h at 0° C. It was diluted with ethyl acetate, washed with H2O, 1N HCl solution, saturated NaHCO3 solution and saturated NaCl solution. The organic layer was dried over MgSO4, filtered and concentrated to dryness. The crude product was purified by silica gel chromatography on a Biotage™ flash chromatography system using a gradient of 0-75% ethyl acetate in CH2Cl2. Tripeptide 74 was obtained as a white solid (546 mg, 98%). 1H NMR (400 MHz, CDCl3) δ 1.44 (s, 9H), 3.10 (d, J=6.8 Hz, 2H), 3.74-3.95 (m, 4H), 4.21 (t, J=7.0 Hz, 1H), 4.40 (d, J=7.2 Hz, 2H), 4.70 (q, J=7.5 Hz, 1H), 5.36 (bs, 1H), 6.31 (bs, 1H), 6.53 (d, J=7.4 Hz, 1H), 7.17-7.22 (m, 3H), 7.24-7.28 (m, 2H), 7.30-7.34 (m, 2H), 7.41 (t, J=7.4 Hz, 2H), 7.59 (d, J=7.3 Hz, 2H), 7.77 (d, J=7.3 Hz, 2H).

Workup

  1. stirringthe reaction mixture was stirred for 2 h at 0° C
  2. washwashed with H2O, 1N HCl solution, saturated NaHCO3 solution and saturated NaCl solution
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe crude product was purified by silica gel chromatography on a Biotage™ flash chromatography system

Sources & evidence

ORD record
ord-26d5495fd7fb40359f9e3e3acc6876d8
Source dataset
uspto-grants-2013_09
Patent number
US08524691B2

Linked notes

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