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Benzyl Alcohol → tert-Butyl [3-(6-amino-1-oxo-3,4-dihydroisoquinolin-2(1H)-yl)propyl]methylcarbamate

HRID 446553
ノート
印刷プレビュー

反応式

HRID 446553 の反応式
[C:1]([O:5][C:6]([N:8]([CH3:27])[CH2:9][CH2:10][CH2:11][N:12]1[CH2:21][CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17](C(OC)=O)[CH:18]=2)[C:13]1=[O:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl.[N-:31]=[N+]=[N-].P([O-])(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.C(N(CC)CC)C.C(O)C1C=CC=CC=1>O1CCCC1.CO.C(OCC)(=O)C>[NH2:31][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:26])[N:12]([CH2:11][CH2:10][CH2:9][N:8]([CH3:27])[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:21][CH2:20]2
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

10

反応物 6

HCID 244Benzyl AlcoholHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 21964642Diphenylphosphate azideHCID 66671432Methyl 2-{3-([tert-butoxycarbonyl)(methyl)amino]propyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxylate

生成物 1

HCID 86663453
tert-Butyl [3-(6-amino-1-oxo-3,4-dihydroisoquinolin-2(1H)-yl)propyl]methylcarbamate
収率 81%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

The compound (535 mg, 1.41 mmol) obtained in Example 61c was dissolved in a mixed solvent (6 mL) of tetrahydrofuran and methanol (1:1), a 1 N aqueous sodium hydroxide solution (1 mL) was added, and the mixture was stirred at 60° C. for 5 hours. After the reaction was completed, a 1 N aqueous hydrochloric acid solution (10 mL) was added to the reaction mixture under ice cooling, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in 1,4-dioxane (6 mL), diphenyl phosphate azide (0.238 mL, 1.10 mmol), triethylamine (0.154 mL, 1.10 mmol) and benzyl alcohol (0.228 mL, 2.21 mmol) were added under ice cooling, and the mixture was stirred at 100° C. under a nitrogen atmosphere for 16 hours. After the reaction was completed, the solvent was evaporated under reduced pressure. The resulting residue was dissolved in a mixed solvent (12 mL) of ethyl acetate and methanol (1:2), 10% palladium-carbon (53 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 1 hour. After the reaction was completed, the reaction mixture was filtered through celite, the filtrate was washed with ethanol, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:methanol, 10:1, v/v) to give the title compound (149 mg; yield, 81%) as a colorless oily substance.

後処理

  1. customto separate the layers
  2. customThe resulting organic layer was separated
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried with anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. dissolutionThe resulting residue was dissolved in 1,4-dioxane (6 mL)
  7. stirringthe mixture was stirred at 100° C. under a nitrogen atmosphere for 16 hours
  8. customthe solvent was evaporated under reduced pressure
  9. dissolutionThe resulting residue was dissolved in a mixed solvent (12 mL) of ethyl acetate and methanol (1:2), 10% palladium-carbon (53 mg)
  10. additionwas added
  11. stirringthe mixture was stirred at room temperature under a hydrogen atmosphere for 1 hour
  12. filtrationthe reaction mixture was filtered through celite
  13. washthe filtrate was washed with ethanol
  14. customthe solvent was evaporated under reduced pressure
  15. customThe residue was purified by NH silica gel column chromatography (ethyl acetate

出典と根拠

ORDレコード
ord-b86280dcbf0649fba3ac6b91d348aa58
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08476253B2

反応ノート

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