Sodium potassium tartrate tetrahydrate → 9-(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-5-bromo-9H-xanthene-3-carboxylic acid diethylamide

HRID 425296ノート

反応式

HRID 425296 の反応式
C(OC([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][C:11](=O)[CH2:12]2)=O)(C)(C)C.[CH2:17]([N:19]([CH2:38][CH3:39])[C:20]([C:22]1[CH:23]=[CH:24][C:25]2[C:26](=O)[C:27]3[C:32]([O:33][C:34]=2[CH:35]=1)=[C:31]([Br:36])[CH:30]=[CH:29][CH:28]=3)=[O:21])[CH3:18].O.O.O.O.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>O1CCCC1.[Zn].[Ti](Cl)(Cl)(Cl)Cl>[CH2:38]([N:19]([CH2:17][CH3:18])[C:20]([C:22]1[CH:23]=[CH:24][C:25]2[C:26](=[C:11]3[CH2:12][CH:13]4[NH:8][CH:9]([CH2:15][CH2:14]4)[CH2:10]3)[C:27]3[C:32]([O:33][C:34]=2[CH:35]=1)=[C:31]([Br:36])[CH:30]=[CH:29][CH:28]=3)=[O:21])[CH3:39]

参加物

7

反応物 3

HCID 2724148Sodium potassium tartrate tetrahydrateHCID 2794767tert-Butyl 3-oxo-8-azabicyclo(3.2.1)octane-8-carboxylateHCID 578392615-Bromo-N,N-diethyl-9-oxo-9H-xanthene-3-carboxamide

生成物 1

HCID 469179409-(8-Aza-bicyclo[3.2.1]oct-3-ylidene)-5-bromo-9H-xanthene-3-carboxylic acid diethylamide収率 73%

試薬・触媒・溶媒 3

HCID 23994Zinc触媒HCID 24193Titanium Tetrachloride触媒HCID 8028Tetrahydrofuran溶媒

実験手順

A suspension of zinc powder (5.59 g, 85.5 mmol) in tetrahydrofuran (THF, 100 mL) at 0° C., was treated with titanium(IV)chloride (4.69 mL, 42.8 mmol) by dropwise addition. The resultant mixture was heated at reflux for 2 h. The resultant solution was cooled to 0° C. 3-oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (2.4 g, 10.7 mmol) and 5-bromo-9-oxo-9H-xanthene-3-carboxylic acid diethylamide (4.0 g, 10.7 mmol) were added and the solution was heated at reflux for 4 h. Potassium sodium tartrate tetrahydrate (30 g, 106 mmol) was added to the reaction mixture and allowed to stir at ambient temperature overnight. The inorganic solids were removed by filtration and washed successively with THF, EtOAc and dichloromethane. The solvent was evaporated in vacuo. Purification by flash chromatography using a gradient 1% to 10% methanol (with ammonia, 2 N) in dichloromethane as the eluent gave Compound 7j (3.65 g). Crude product was purified by reverse phase preparative HPLC, using a gradient of acetonitrile (10% to 90%) in water with trifluoroacetic acid (0.1%), to give the trifluoroacetic acid salt of compound 7j. MS: m/z 467.0 (MH+). 1H NMR (DMSO-d6): δ 1.0-1.2 (br m, 6H), 1.32 (d, 2H, J=7.9 Hz), 1.75-1.85 (br m, 2H), 2.85-3.10 (m, 4H), 3.15-3.50 (br m, 4H), 4.01 br s, 2H), 7.15-7.26 (m, 3H), 7.42 (d, 1H, J=6.7 Hz), 7.49 (d, 1H, J=7.9 Hz), 7.66 (d, 1H, J=7.9 Hz), 8.81 (br s, 1H) and 9.12 br d, 1H).

後処理

  1. temperatureat reflux for 2 h
  2. temperaturethe solution was heated
  3. temperatureat reflux for 4 h
  4. customThe inorganic solids were removed by filtration
  5. washwashed successively with THF, EtOAc and dichloromethane
  6. customThe solvent was evaporated in vacuo
  7. customPurification by flash chromatography

出典と根拠

ORDレコード
ord-7244e98f4f15495cb30988082bf1ec88
出典データセット
uspto-grants-2012_01
特許番号
US08106207B2

反応ノート

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