Methanol → 7-Hydroxymethyl-10-oxo-1,3,4,9,10,10a-hexahydro-2,4-a,5,9-tetraaza-phenanthrene-2-carboxylic acid tert-butyl ester

HRID 69674

反応式

HRID 69674 の反応式
C[O:2][C:3]([C:5]1[CH:18]=[C:17]2[C:8]([N:9]3[CH:14]([C:15](=[O:19])[NH:16]2)[CH2:13][N:12]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:11][CH2:10]3)=[N:7][CH:6]=1)=O.[H-].[Na+].[H-].[Al+3].[Li+].[H-].[H-].[H-].CO>O1CCCC1.O.C(OCC)(=O)C>[C:23]([O:22][C:20]([N:12]1[CH2:11][CH2:10][N:9]2[CH:14]([C:15](=[O:19])[NH:16][C:17]3[C:8]2=[N:7][CH:6]=[C:5]([CH2:3][OH:2])[CH:18]=3)[CH2:13]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

参加物

8

反応物 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 21226445Aluminium lithium hydrideHCID 5832446410-Oxo-1,3,4,9,10,10a-hexahydro-2,4-a,5,9-tetraaza-phenanthrene-2,7-dicarboxylic acid 2-tert-butyl ester 7-methyl ester

生成物 1

HCID 583244417-Hydroxymethyl-10-oxo-1,3,4,9,10,10a-hexahydro-2,4-a,5,9-tetraaza-phenanthrene-2-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
-45 °C

実験手順

10-Oxo-1,3,4,9,10,10a-hexahydro-2,4a,5,9-tetraaza-phenanthrene-2,7-dicarboxylic acid 2-tert-butyl ester 7-methyl ester (545 mg, 1.504 mmol) was taken up in tetrahydrofuran (18 mL) in an inert environment. To the stirred suspension at room temperature was added NaH (90 mg, 2.26 mmol, 60% dispersion in mineral oil) and stirred 30 minutes. The reaction was then cooled to −45° C. and lithium aluminum hydride (2.26 ml, 2M in THF) was added. The reaction was stirred at a temperature between −20 and −10° C. for 1 hour. The reaction was then cooled back to −60° C. and MeOH (5 ml) followed by water (1 ml) was added. The reaction was allowed to stir at ambient temperature for 2 hours and then poured into ethyl acetate (400 ml) and water (100 ml). The biphasic mixture was stirred vigorously and then filtered through a medium frit. The filtrate was collected. The layers were separated and the aqueous phase was extracted with ethyl acetate (1×100 ml). The organic layers were combined, washed with brine (100 ml), and concentrated to 429.4 mg (96%) of the title compound as an off-white solid. [M+H] calc'd for C16H22N4O4, 335; found, 335

後処理

  1. stirringThe reaction was stirred at a temperature between −20 and −10° C. for 1 hour
  2. temperatureThe reaction was then cooled back to −60° C.
  3. additionwas added
  4. stirringto stir at ambient temperature for 2 hours
  5. stirringThe biphasic mixture was stirred vigorously
  6. filtrationfiltered through a medium frit
  7. customThe filtrate was collected
  8. customThe layers were separated
  9. extractionthe aqueous phase was extracted with ethyl acetate (1×100 ml)
  10. washwashed with brine (100 ml)
  11. concentrationconcentrated to 429.4 mg (96%) of the title compound as an off-white solid

出典と根拠

ORDレコード
ord-b5363c0194d74c959063ab7294e0c48f
出典データセット
uspto-grants-2014_09
特許番号
US08822470B2

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