Oxalyl chloride → HCID 67211736、化合物

HRID 1401886ノート

反応式

HRID 1401886 の反応式
[C:1]([O:5][C:6](=[O:34])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH2:29][CH2:28][C@@H:27]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:26][CH:25]=3)=[CH:20][CH:19]=2)[C:15](O)=[O:16])=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[Cl:41][C:42]1(N)[CH:47]=[CH:46][C:45]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[C:44]([CH3:54])[CH2:43]1.CC[N:58](C(C)C)C(C)C>ClCCl.CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:34])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH2:29][CH2:28][C@@H:27]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:26][CH:25]=3)=[CH:20][CH:19]=2)[C:15](=[O:16])[NH:58][C:51]2[CH:52]=[CH:53][C:48]([C:45]3[CH:46]=[CH:47][C:42]([Cl:41])=[CH:43][C:44]=3[CH3:54])=[CH:49][CH:50]=2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

8

反応物 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 67211535HCID 67211535、化合物HCID 71238554HCID 71238554、化合物

生成物 1

HCID 67211736HCID 67211736、化合物収率 59%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To 4-{2-[4-(4-(R)-tert-Butylcyclohex-1-enyl)-phenyl]-2-carboxy-ethyl}-benzoic acid tert-butyl ester (697 mg, 1.51 mmol) in anhydrous dichloromethane (30 mL) was added oxalyl chloride (650 uL, 7.53 mmol) and 3 drops of DMF. The resulting solution was stirred at rt for 1 hr before being concentrated under vacuum. The residue was co-evaporated with toluene (1×5 mL) then dissolved in toluene again (20 mL). To the mixture was added 4-chloro-2-methylbiphenyl-4-ylamine (361 mg, 1.66 mmol) and DIPEA (1.3 mL, 7.53 mmol). The resulting mixture was refluxed for 90 min, diluted with ethyl acetate and washed with saturated NaHCO3. The organic portion was dried over Na2SO4 and concentrated under vacuum to afford crude material which was crystallized from MeOH to afford a white solid (590 mg). Removing the solvent and purification of the residue by chromatography on silica gel using an ethyl acetate/hexanes gradient afforded an additional 137 mg of product. 1H NMR (500 MHz, DMSO-d6): 10.16 (s, 1H), 7.78 (d, J=8 Hz, 2 H), 7.59 (d, J=8.5 Hz, 2 H), 7.4-7.32 (m, 7 H), 7.21 (d, J=8 Hz, 2 H), 7.15 (d, J=8 Hz, 2 H), 6.14 (m, 1H), 4.03 (dd, J=9, 7 Hz, 1 H), 3.48 (dd, J=13.5, 9.5 Hz, 1 H), 3.41 (dd, J=13.5, 6.5 Hz, 1 H), 2.4-2.3 (m, 1H), 2.2-2.15 (m, 4H), 1.96-1.9 (m, 2H), 1.52 (s, 9 H), 1.32-1.2 (m, 2 H), 0.89 (s, 9H).

後処理

  1. concentrationbefore being concentrated under vacuum
  2. dissolutionthen dissolved in toluene again (20 mL)
  3. temperatureThe resulting mixture was refluxed for 90 min
  4. washwashed with saturated NaHCO3
  5. dry with materialThe organic portion was dried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customto afford crude material which
  8. customwas crystallized from MeOH

出典と根拠

ORDレコード
ord-8fc06f2a0adf4c2b8fa4e7c5a4146ca4
出典データセット
uspto-grants-2014_12
特許番号
US08907103B2

反応ノート

読み込み中…