Citric Acid → 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-((tert-butoxycarbonyl)amino)benzamido)methyl)benzoic acid

HRID 923604ノート

反応式

HRID 923604 の反応式
[CH:1]([O-:3])=[O:2].[Li+].CCN(C(C)C)C(C)C.C(OC(=O)C)(=O)C.Br[C:22]1[CH:53]=[CH:52][C:25]([CH2:26][N:27]([CH2:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[C:28](=[O:43])[C:29]2[CH:34]=[CH:33][C:32]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:31][CH:30]=2)=[CH:24][CH:23]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:48]([O:47][C:45](=[O:46])[CH2:44][N:27]([CH2:26][C:25]1[CH:52]=[CH:53][C:22]([C:1]([OH:3])=[O:2])=[CH:23][CH:24]=1)[C:28](=[O:43])[C:29]1[CH:34]=[CH:33][C:32]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[CH:31][CH:30]=1)([CH3:51])([CH3:50])[CH3:49]

参加物

8

反応物 5

HCID 311Citric AcidHCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 23680280Lithium formateHCID 71076642tert-butyl 2-(N-(4-bromobenzyl)-4-((tert-butoxycarbonyl)amino)benzamido)acetate

生成物 1

HCID 711120664-((N-(2-(tert-butoxy)-2-oxoethyl)-4-((tert-butoxycarbonyl)amino)benzamido)methyl)benzoic acid収率 79%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
120 °C

実験手順

Prepared using General Procedure 21. To a stirred suspension of lithium formate (1.19 g, 22.9 mmol) in DMF (10 mL) was added DIEA (2.67 mL, 15.3 mmol) and acetic anhydride (1.44 mL, 15.3 mmol) at room temperature. After 30 min the reaction mixture was purged with N2 and a solution of tert-butyl 2-(N-(4-bromobenzyl)-4-((tert-butoxycarbonyl)amino)benzamido)acetate INT-61 (3.97 g, 7.64 mmol) and PdCl2(dppf) (0.559 g, 0.764 mmol) in DMF (5 mL) was added. The reaction mixture was heated for 1 h at 120° C. The reaction mixture was poured onto 1 M citric acid (200 mL) and extracted with EA (200 mL). The organics were washed with brine (200 mL), dried over MgSO4 and concentrated in vacuo. The crude product was purified by chromatography (1% AcOH in EA/hexanes) to afford 2.92 g (79%) of 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-((tert-butoxycarbonyl)amino)benzamido)methyl)benzoic acid INT-62 as a red-tinged foam. LCMS-ESI (m/z) calculated for C26H32N2O7: 484; found 430 [M-t-Bu+H]+, tR=2.23 min (Method 10).

後処理

  1. customPrepared
  2. customAfter 30 min the reaction mixture was purged with N2
  3. extractionextracted with EA (200 mL)
  4. washThe organics were washed with brine (200 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by chromatography (1% AcOH in EA/hexanes)

出典と根拠

ORDレコード
ord-3811e95588264f7f9ff2e474ecd532e3
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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