Aniline → Z-Trp-NHPh

HRID 2074344Notes

Reaction equation

HRID 2074344 reaction equation
[NH:1]([C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C@H:2]([C:13]([OH:15])=O)[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[NH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[NH:1]([C:16]([O:18][CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[O:17])[C@H:2]([C:13]([NH:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:15])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1

Participants

5

Reactant 3

HCID 6115AnilineHCID 10868DicyclohexylcarbodiimideHCID 101176benzyloxycarbonyl-L-tryptophan

Product 1

HCID 1131238Z-Trp-NHPhYield 69.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Z-Trp-OH (2 g, 5.9 mmol) in THF (88 mL) at 5° C. were added aniline (540 μL, 5.9 mmol) and DCC (1.6 g, 7.7 mmol). The reaction was allowed to warn up to room temperature overnight. The solvent was evaporated off and the crude was triturated with ethyl acetate (50 mL). After filtration, the organic phase was successively washed with aqueous 5% KHSO4, aqueous 10% KHCO3, brine and was dried over Na2SO4. The solvent was removed in vacuo. The crude amide was purified by precipitation in methanol/pentane to give a white amorphous solid (1.7 g, 69%). 1H NMR (300 MHz, CDCl3) δ 3.25 (dd, J=14.4 Hz, J=8 Hz, 1H, CH2), 3.46 (dd, J=14.4 Hz, J=5.3 Hz, 1H, CH2), 4.67 (m, 1H, CHα), 5.12 (m, 2H, CH2 (Z)), 5.63 (broad s, 1H, NHZ), 7.06-7.72 (m, 16H, 15 aromatic H, NH amide), 8.09 (s, 1H, NH indole). 13C NMR (75 MHz, CDCl3) δ 28.6 (CH2 Trp), 56.1 (CHα), 67.2 (CH2 (Z)), 111.4, 118.8, 119.9, 120.1, 122.4, 123.4, 124.5, 127.1, 128.1, 128.3, 128.6, 128.9, 136, 136.2, 137.1 (20 aromatic C), 156 (CO carbamate), 169.7 (CO amide). Anal. Calcd. for C25H23N3O3: C, 72.62; H, 5.61; N, 10.16. Found: C, 72.75; H, 5.58; N, 9.95.

Workup

  1. customThe solvent was evaporated off
  2. customthe crude was triturated with ethyl acetate (50 mL)
  3. filtrationAfter filtration
  4. washthe organic phase was successively washed with aqueous 5% KHSO4, aqueous 10% KHCO3, brine
  5. dry with materialwas dried over Na2SO4
  6. customThe solvent was removed in vacuo
  7. customThe crude amide was purified by precipitation in methanol/pentane

Sources & evidence

ORD record
ord-87589d2020aa4415a199c5f7d40f3f5f
Source dataset
uspto-grants-2011_04
Patent number
US07919468B2

Reaction notes

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