Water → Ammonia

HRID 1433252ノート

反応式

HRID 1433252 の反応式
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[C@@H:16]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:17][CH2:18][N:19]([CH:23]([CH3:25])[CH3:24])[CH:20]([CH3:22])[CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:32](=[O:35])([O-:34])[O-].[Cs+].[Cs+].[C:38]([O:42][C:43](=[O:53])[NH:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51]Br)([CH3:41])([CH3:40])[CH3:39].O>CN(C)C=O.[Cl-].[Na+].O>[NH3:19].[C:2]([O:34][C:32]([N:44]([CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][O:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:10]([C@@H:16]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:17][CH2:18][N:19]([CH:20]([CH3:22])[CH3:21])[CH:23]([CH3:24])[CH3:25])[CH:11]=1)[C:43]([O:42][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:53])=[O:35])([CH3:7])([CH3:3])[CH3:1]

参加物

8

反応物 4

HCID 962WaterHCID 10796Cesium carbonate3 回HCID 10108474tert-butyl N-(7-bromoheptyl)carbamate3 回HCID 579331854-(Benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol

生成物 2

HCID 222AmmoniaHCID 69008693Di-tert-butyl(7-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenoxy}heptyl)imidodicarbonate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 57417360Sodium chloride; water溶媒

実験手順

4-(Benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol (Preparation 16, 150 mg, 0.36 mmol) was dissolved in dimethylformamide (2 ml), caesium carbonate (140 mg, 0.43 mmol) was added and stirred at room temperature for 30 minutes. tert-Butyl(7-bromoheptyl)carbamate (Prepared according to J. Med. Chem., 1994, 137, p2537-2551; 170 mg, 0.43 mmol), dissolved in dimethylformamide (1 ml), was added and heated to 70oC. After 2.5 hours caesium carbonate (70 mg, 0.22 mmol) was added and after a further 10 minutes tert-butyl(7-bromoheptyl)carbamate (70 mg, 0.18 mmol) was added. After 1 hour caesium carbonate (20 mg, 0.06 mmol) and tert-butyl(7-bromoheptyl)carbamate (35 mg, 0.09 mmol) were added and after 1 hour at 70° C. the mixture was cooled to room temperature and stirred for 3 days before the addition of water and brine were added, the mixture extracted with ethyl acetate, dried (magnesium sulphate), filtered and the solvents removed in vacuo and the residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (98/2/0.2 to 95/5/0.5 by volume) to furnish the title compound as a colourless gum, 220 mg.

後処理

  1. additionwas added
  2. temperatureheated to 70oC
  3. additionwas added
  4. temperaturewas cooled to room temperature
  5. additionwere added
  6. extractionthe mixture extracted with ethyl acetate
  7. dry with materialdried (magnesium sulphate)
  8. filtrationfiltered
  9. customthe solvents removed in vacuo
  10. customthe residue was purified by column chromatography on silica gel eluting with dichloromethane

出典と根拠

ORDレコード
ord-34bb0e0b25ff42a18a2d6a8be1db03ff
出典データセット
uspto-grants-2009_11
特許番号
US07612084B2

反応ノート

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