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

HRID 923540Notes

Reaction equation

HRID 923540 reaction equation
[CH2:1]([O:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(Cl)(=O)C(Cl)=O.O[C:24]1[CH:59]=[CH:58][C:27]([CH2:28][N:29]([CH2:50][C:51]([O:53]C(C)(C)C)=[O:52])[C:30](=[O:49])[C:31]2[CH:36]=[CH:35][C:34]([NH:37][C:38](=[O:48])[CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)=[CH:33][CH:32]=2)=[CH:26][CH:25]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.CN(C=O)C>[CH2:1]([O:7][C:8]1[CH:9]=[CH:10][C:11]([C:12]([O:14][C:24]2[CH:59]=[CH:58][C:27]([CH2:28][N:29]([CH2:50][C:51]([OH:53])=[O:52])[C:30](=[O:49])[C:31]3[CH:32]=[CH:33][C:34]([NH:37][C:38](=[O:48])[CH2:39][C:40]4[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=4)=[CH:35][CH:36]=3)=[CH:26][CH:25]=2)=[O:13])=[CH:15][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 65578Oxalyl chlorideHCID 708344-(Hexyloxy)benzoic acidHCID 71076654tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate

Product 1

HCID 892530842-(N-(4-((4-(hexyloxy)benzoyl)oxy)benzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido) acetic acidYield 35%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Prepared using General Procedures 2 and 8: To a stirring solution of 4-(hexyloxy)benzoic acid (26 mg, 0.119 mmol) in DCM (0.5 mL) were added DMF (1 drop) and oxalyl chloride (0.011 mL, 0.127 mmol). The reaction mixture was stirred at room temperature for 30 min. To this mixture was added a solution of tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate INT-7 (40 mg, 0.079 mmol) and TEA (0.022 mL, 0.159 mmol) in DCM (1 mL). The reaction was stirred at room temperature for 2 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 yield 18.2 mg (35%) of 2-(N-(4-((4-(hexyloxy)benzoyl)oxy)benzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido) acetic acid 18. LCMS-ESI (m/z) calculated for C38H40N2O8: 652; found 651 [M−H]−, tR=9.01 min (Method 4). 1H NMR (400 MHz, DMSO) δ 12.80 (s, 1H), 10.25 (s, 1H), 8.10-7.99 (m, 2H), 7.68-7.62 (m, 2H), 7.50-7.19 (m, 8H), 7.17-7.07 (m, 2H), 6.91-6.84 (m, 2H), 4.70-4.54 (d, J=35.9 Hz, 2H), 4.12-4.04 (t, J=6.5 Hz, 2H), 4.00-3.86 (d, J=34.1 Hz, 2H), 3.72 (s, 3H), 3.56 (s, 2H), 1.79-1.69 (m, 2H), 1.47-1.38 (m, 2H), 1.37-1.28 (ddd, J=7.6, 3.9, 2.1 Hz, 4H), 0.91-0.84 (m, 3H).

Workup

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

Sources & evidence

ORD record
ord-3ab0447aa33d4ff1a9b9b057aec9798c
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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