Trifluoroacetic acid → 2-(N-(4-(([1,1'-biphenyl]-4-carbonyl)oxy)benzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetic acid

HRID 923541Notes

Reaction equation

HRID 923541 reaction equation
[OH:1][C:2]1[CH:37]=[CH:36][C:5]([CH2:6][N:7]([CH2:28][C:29]([O:31]C(C)(C)C)=[O:30])[C:8](=[O:27])[C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:26])[CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[C:38]1([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:43]=[CH:42][C:41]([C:44](Cl)=[O:45])=[CH:40][CH:39]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:38]1([C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:39]=[CH:40][C:41]([C:44]([O:1][C:2]2[CH:37]=[CH:36][C:5]([CH2:6][N:7]([CH2:28][C:29]([OH:31])=[O:30])[C:8](=[O:27])[C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:16](=[O:26])[CH2:17][C:18]4[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=4)=[CH:13][CH:14]=3)=[CH:4][CH:3]=2)=[O:45])=[CH:42][CH:43]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 841514-Phenylbenzoyl chlorideHCID 71076654tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate

Product 1

HCID 714887482-(N-(4-(([1,1'-biphenyl]-4-carbonyl)oxy)benzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetic acidYield 25%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedures 2 and 8: To a stirring 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) were added [1,1′-biphenyl]-4-carbonyl chloride (26 mg, 0.119 mmol). The reaction was stirred 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 afford 12.5 mg (25%) of 2-(N-(4-(([1,1′-biphenyl]-4-carbonyl)oxy)benzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetic acid 32. LCMS-ESI (m/z) calculated for C38H32N2O7: 629; found 628 [M−H]−, tR=7.83 min (Method 4). NMR (400 MHz, DMSO) δ 10.31 (s, 1H), 8.21 (d, J=8.1 Hz, 2H), 7.92 (d, J=8.4 Hz, 3H), 7.79 (d, J=7.7 Hz, 2H), 7.65 (d, J=8.2 Hz, 2H), 7.58-7.41 (m, 4H), 7.41-7.17 (m, 6H), 6.88 (d, J=8.2 Hz, 2H), 4.64 (d, J=36.7 Hz, 2H), 3.95 (d, J=33.6 Hz, 2H), 3.72 (s, 3H), 3.57 (s, 2H).

Workup

  1. customPrepared
  2. stirringAfter stirring for 2 h
  3. concentrationthe solvent was concentrated
  4. customthe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-15107ea6e1bb415d8df7a87dcb96b6d7
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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