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

HRID 923548ノート

反応式

HRID 923548 の反応式
C[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[C:17](Cl)(=O)[C:18](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(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C.O>[CH3:47][O:46][C:43]1[CH:42]=[CH:41][C:40]([CH2:39][C:38]([NH:37][C:34]2[CH:33]=[CH:32][C:31]([C:30]([N:29]([CH2:50][C:51]([OH:53])=[O:52])[CH2:28][C:27]3[CH:26]=[CH:25][C:24]([O:16][C:14](=[O:15])[C:11]4[CH:10]=[CH:9][C:8]([CH2:5][CH2:6][CH2:7][CH2:2][CH2:3][CH2:4][CH2:17][CH3:18])=[CH:13][CH:12]=4)=[CH:59][CH:58]=3)=[O:49])=[CH:36][CH:35]=2)=[O:48])=[CH:45][CH:44]=1

参加物

8

反応物 3

HCID 65578Oxalyl chlorideHCID 20634214'-Methyl-4-biphenylcarboxylic acidHCID 71076654tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate

生成物 1

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

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide触媒HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

Prepared using General Procedures 2 then 8: To a stirring solution of 4′-methyl-[1,1′-biphenyl]-4-carboxylic acid (334 mg, 1.57 mmol) in DCM (10 mL) were added DMF (5 drops) and oxalyl chloride (0.14 mL, 1.68 mmol). The reaction mixture was stirred at room temperature for 1 h. To this mixture was added a solution of tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate INT-9 (750 mg, 1.31 mmol) and TEA (0.37 mL, 2.62 mmol) in DCM (10 mL). The reaction mixture was stirred at room temperature for 1 h then DMAP (30 mg, 0.33 mmol) was added. After a further 2 h at room temperature, the reaction was diluted with DCM (50 mL) and washed with NaHCO3 (50 mL). The organics were pre-absorbed onto silica gel and purified by chromatography (EA/isohexanes). The isolated material was taken up into DCM (10 mL) and TFA (5 mL) was added. After 2 h the solvent was removed under vacuum and solid was evaporated from diethyl ether (5 mL) and isohexanes (20 mL) to give a fine powdery solid. Trituration from DCM/isohexanes and isolation by filtration gave a fine powder that was slurried in water (20 mL) and isolated by filtration. The solid was washed with DCM and isohexanes (9:1, 50 mL) followed by isohexanes (50 mL) to afford 15.3 mg (19%) of 2-(4-(2-(4-methoxyphenyl)acetamido)-N-(4-((4-octylbenzoyl)oxy)benzyl)benzamido)acetic acid 192. LCMS-ESI (m/z) calculated for C40H33F3N2O7: 710; found 711 [M+H]+, tR=8.81 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.96-12.60 (br s, 1H), 10.36 (s, 1H), 8.25-8.16 (m, 2H), 7.94-7.84 (m, 2H), 7.75-7.62 (m, 4H), 7.55-7.27 (m, 9H), 7.25-7.15 (m, 2H), 4.70 (s, 1H), 4.61 (s, 1H), 4.03 (s, 1H), 3.95 (s, 1H), 3.8-3.78 (m, 5H), 2.37 (s, 3H).

後処理

  1. customPrepared
  2. stirringThe reaction mixture was stirred at room temperature for 1 h
  3. waitAfter a further 2 h at room temperature
  4. washwashed with NaHCO3 (50 mL)
  5. customThe organics were pre-absorbed onto silica gel
  6. custompurified by chromatography (EA/isohexanes)
  7. additionwas added
  8. customAfter 2 h the solvent was removed under vacuum and solid
  9. customwas evaporated from diethyl ether (5 mL) and isohexanes (20 mL)
  10. customto give a fine powdery solid
  11. filtrationTrituration from DCM/isohexanes and isolation by filtration
  12. customgave a fine powder that
  13. customisolated by filtration
  14. washThe solid was washed with DCM and isohexanes (9:1, 50 mL)

出典と根拠

ORDレコード
ord-806bbfd52a044bd1b495d6d77a21feba
出典データセット
uspto-grants-2016_03
特許番号
US09278910B2

反応ノート

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