Oxalyl chloride → HCID 57501581、化合物

HRID 1518660ノート

反応式

HRID 1518660 の反応式
[P:1]([O-])([O:11][CH2:12][C:13]1C=CC=CC=1)([O:3][CH2:4][C:5]1C=CC=CC=1)=[O:2].C(Cl)(=O)C(Cl)=O.[CH2:26]1[N:31]([CH2:32][CH2:33][CH2:34][CH2:35][O:36][C:37]2[CH:42]=[CH:41][C:40]3[CH:43]=[CH:44][C:45]([NH:47][C:39]=3[CH:38]=2)=[O:46])[CH2:30][CH2:29][N:28]([C:48]2[CH:53]=[CH:52][CH:51]=[C:50]([Cl:54])[C:49]=2[Cl:55])[CH2:27]1.CC(C)([O-])C.[K+]>ClCCl.CN(C)C=O>[P:1]([O:11][CH2:12][CH3:13])([O:3][CH2:4][CH3:5])([O:46][C:45]1[CH:44]=[CH:43][C:40]2[C:39](=[CH:38][C:37]([O:36][CH2:35][CH2:34][CH2:33][CH2:32][N:31]3[CH2:30][CH2:29][N:28]([C:48]4[CH:53]=[CH:52][CH:51]=[C:50]([Cl:54])[C:49]=4[Cl:55])[CH2:27][CH2:26]3)=[CH:42][CH:41]=2)[N:47]=1)=[O:2]

参加物

7

反応物 4

HCID 65578Oxalyl chlorideHCID 4193600DibenzylphosphateHCID 10114519DehydroaripiprazoleHCID 23665647Potassium tert-butoxide

生成物 1

HCID 57501581HCID 57501581、化合物

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of dibenzyl phosphate (2.48 g, 8.91 mmol) in dichloromethane (25 ml) was added N,N-dimethyl formamide (1 drop) followed by oxalyl chloride (0.75 mL, 8.91 mmol). After 2 hours the reaction mixture was concentrated in vacuo. The residue was dissolved in 2-methyltetrahydrfuran (5 mL) and added to a suspension of dehydro-aripiprazole (1.66 g, 3.71 mmol) and potassium t-butoxide (0.92 g, 8.17 mmol) in 2-methyltetrahydrfuran (35 mL) at 0° C. under argon gas, then allowed to gradually warm to room temperature. After stirring overnight the reaction was quenched with water (25 mL) and 28% aq NH3 (15 mL) and stirred for 10 minutes. The reaction mixture was then extracted with ethyl acetate (2×40 mL). The combined organics were washed with water (50 mL) and brine (50 mL) then dried (MgSO4) and concentrated in vacuo. The crude mixture was purified by column chromatography eluting with 5% methanol (1:1 ethyl acetate/dichloromethane) to give the product. The 1H-NMR showed minor impurities still present (impurities not observed by LCMS). Various further purifications were attempted but failed to remove these impurities.

後処理

  1. concentrationAfter 2 hours the reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved in 2-methyltetrahydrfuran (5 mL)
  3. customwas quenched with water (25 mL) and 28% aq NH3 (15 mL)
  4. stirringstirred for 10 minutes
  5. extractionThe reaction mixture was then extracted with ethyl acetate (2×40 mL)
  6. washThe combined organics were washed with water (50 mL) and brine (50 mL)
  7. dry with materialthen dried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe crude mixture was purified by column chromatography
  10. washeluting with 5% methanol (1:1 ethyl acetate/dichloromethane)
  11. customto give the product
  12. customto remove these impurities

出典と根拠

ORDレコード
ord-10e6b9d31115409a9c134e705e92bd90
出典データセット
uspto-grants-2015_07
特許番号
US09072788B2

反応ノート

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