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Isoindoline → N-{2-Chloro-4-[(1-isopropyl-4-piperidinyl)oxy]benzoyl}isoindoline hydrochloride

HRID 268741
ノート
印刷プレビュー

反応式

HRID 268741 の反応式
Cl.[Cl:2][C:3]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH:19]([CH3:21])[CH3:20])[CH2:15][CH2:14]2)[CH:9]=[CH:8][C:4]=1[C:5](Cl)=[O:6].CC[N:24]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:25]C.C=CC1C=CC=CC=1.C=CC1C=CC(C=C)=CC=1.C1C2C(=CC=CC=2)CN1>C(Cl)Cl>[ClH:2].[Cl:2][C:3]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH:19]([CH3:21])[CH3:20])[CH2:15][CH2:14]2)[CH:9]=[CH:8][C:4]=1[C:5]([N:24]1[CH2:25][C:29]2[C:28](=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:27]1)=[O:6]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 422478IsoindolineHCID 16212021N-benzyl-N-ethylethanamine;1,4-bis(ethenyl)benzene;styreneHCID 179862952-Chloro-4-[(1-isopropyl-4-piperidinyl)oxy]benzoyl chloride hydrochloride

生成物 1

HCID 17986276N-{2-Chloro-4-[(1-isopropyl-4-piperidinyl)oxy]benzoyl}isoindoline hydrochloride収率 72.9%

試薬・触媒・溶媒 1

HCID 6344
Dichloromethane
溶媒

実験手順

A stirred mixture of 2-chloro-4-[(1-isopropyl-4-piperidinyl)oxy]benzoyl chloride hydrochloride (D33) (0.20 g) and diethylaminomethyl polystyrene (3.2 mmol/g, 1.0 g) in DCM (10 ml) at rt was treated with isoindoline (0.08 g) and stirred for 16 h. The reaction mixture was chromatographed directly [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM]. Fractions containing the required product were evaporated, redissolved in DCM, treated with excess hydrogen chloride (1M solution in diethyl ether) and then concentrated. The residue was crystallised from acetone to yield the title compound (E62) as a white solid (0.09 g). MS electrospray (+ion) 399/401 (MH+). 1H NMR δ (DMSO-d6): 10.90 (1H, s), 7.33-7.10 (6H, m), 6.96 (1H, m), 4.82-4.51 (3H, m), 4.39 (3H, m), 3.35 (2H, m), 3.00 (2H, m), 2.11-1.80 (4H, m), 1.17 (6H, m).

後処理

  1. customThe reaction mixture was chromatographed directly [silica gel, step gradient 0-10% MeOH (containing 10% 0.880 ammonia solution) in DCM]
  2. additionFractions containing the required product
  3. customwere evaporated
  4. dissolutionredissolved in DCM
  5. additiontreated with excess hydrogen chloride (1M solution in diethyl ether)
  6. concentrationconcentrated
  7. customThe residue was crystallised from acetone

出典と根拠

ORDレコード
ord-3fa3325b86b7444ead87de07ed6935a5
出典データセット
uspto-grants-2008_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07446103B2

反応ノート

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