Trifluoroacetic acid → 2-(4-(2-(4-methoxyphenyl)acetamido)-N-(4-((4-octylbenzoyl)oxy)benzyl)benzamido)acetic acid

HRID 923543Notes

Reaction equation

HRID 923543 reaction equation
[CH2:1]([C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C(Cl)(=O)C(Cl)=O.O[C:25]1[CH:60]=[CH:59][C:28]([CH2:29][N:30]([CH2:51][C:52]([O:54]C(C)(C)C)=[O:53])[C:31](=[O:50])[C:32]2[CH:37]=[CH:36][C:35]([NH:38][C:39](=[O:49])[CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=3)=[CH:34][CH:33]=2)=[CH:27][CH:26]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.CN(C=O)C>[CH3:48][O:47][C:44]1[CH:43]=[CH:42][C:41]([CH2:40][C:39]([NH:38][C:35]2[CH:34]=[CH:33][C:32]([C:31]([N:30]([CH2:51][C:52]([OH:54])=[O:53])[CH2:29][C:28]3[CH:27]=[CH:26][C:25]([O:14][C:13](=[O:15])[C:12]4[CH:11]=[CH:10][C:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])=[CH:17][CH:16]=4)=[CH:60][CH:59]=3)=[O:50])=[CH:37][CH:36]=2)=[O:49])=[CH:46][CH:45]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 19147p-Octylbenzoic acidHCID 65578Oxalyl chlorideHCID 71076654tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate

Product 1

HCID 714887742-(4-(2-(4-methoxyphenyl)acetamido)-N-(4-((4-octylbenzoyl)oxy)benzyl)benzamido)acetic acidYield 19%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Prepared using General Procedures 2 and 8: To a stirring solution of 4-octylbenzoic acid (42 mg, 0.178 mmol) in DCM (0.5 mL) were added DMF (1 drop) and oxalyl chloride (0.016 mL, 0.190 mmol). The reaction mixture was stirred at room temperature for 2 h. To this mixture was added a solution of tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate INT-7 (60 mg, 0.119 mmol) and TEA (0.050 mL, 0.357 mmol) in DCM (1 mL). The reaction was stirred at room temperature for 18 h then TFA (1 mL) was added. After stirring for 2 h, the solvent was concentrated and the product was purified by preparative HPLC to provide to afford 15.3 mg (19%) of 2-(4-(2-(4-methoxyphenyl)acetamido)-N-(4-((4-octylbenzoyl)oxy)benzyl)benzamido)acetic acid 40. LCMS-ESI (m/z) calculated for C40H44N2O7: 664; found 665 [M+H]+, tR=10.33 min (Method 4). 1H NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.04 (d, J=8.2 Hz, 2H), 7.65 (d, J=8.5 Hz, 2H), 7.50-7.21 (m, 10H), 6.89 (d, J=8.4 Hz, 2H), 4.63 (d, J=36.7 Hz, 2H), 3.95 (d, J=33.1 Hz, 2H), 3.73 (s, 3H), 3.58 (s, 2H), 2.76-2.64 (m, 2H), 1.61 (s, 2H), 1.36-1.10 (m, 10H), 0.86 (t, J=6.8 Hz, 3H).

Workup

  1. customPrepared
  2. stirringThe reaction was stirred at room temperature for 18 h
  3. stirringAfter stirring for 2 h
  4. concentrationthe solvent was concentrated
  5. customthe product was purified by preparative HPLC
  6. customto provide

Sources & evidence

ORD record
ord-9901a10fbb354ead92f098ad0bcf3983
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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