tert-Butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylate → N'-(3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-N'-(4-pyridin-2-yl-benzyl)-hydrazinecarboxylic acid tert-butyl ester

HRID 514603ノート

反応式

HRID 514603 の反応式
[C:1]([O:5][C:6]([NH:8][NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:23]1[C@@H:25]([C@@H:26]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:24]1>CC(O)C>[C:1]([O:5][C:6]([NH:8][N:9]([CH2:24][CH:25]([OH:23])[CH:26]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

4

反応物 2

HCID 9796325tert-Butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylateHCID 9903372(2S,3S)-(-)-3-tert-Butoxycarbonylamino-1,2-epoxy-4-phenylbutane

生成物 1

HCID 10940720N'-(3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-N'-(4-pyridin-2-yl-benzyl)-hydrazinecarboxylic acid tert-butyl ester収率 66%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

Into a 100 mL flask was placed (5) (1.0 g, 3.34 mmol), (6) (2S,3S)-1,2-epoxy-3-(Boc-amino)-4-phenylbutane (2.78 g, 10.5 mmol, 3.16 equivalents), and 2-propanol (15 mL). The reaction was heated to reflux. After approximately 61 hours of refluxing, the heat was removed, and the mixture cooled to room temperature. To the cooled mixture was added water/ice (50 mL). To the aqueous mixture was added dichloromethane (50 mL) and then transferred to a separatory funnel. The aqueous layer was extracted with dichloromethane (3×50 mL). The combined organics were washed with water, then saturated sodium chloride, and then dried over sodium sulfate. The dried organic solution was filtered, and the filtrate was concentrated under reduced pressure, and then dried under high vacuum overnight. The yellow foam was purified by Biotage chromatography (40+M cartridge; 0 to 5% methanol/dichloromethane over 25 CV) to give 1.24 g (66%) of (7) as a white solid. TLC Rf (hexane/ethyl acetate, 1:2)=0.45; 1H NMR (CD3OD) δ 8.60 (d, 1H), 7.88 (m 4H), 7.50 (d, 2H), 7.36 (m, 1H), 7.25 (m, 4H), 7.18 (m, 1H), 3.93 (m, 2H), 3.70 (m, 2H), 3.0-2.6 (m, 4H), 1.33 (s, 9H), 1.30 (s, 9H); MS (M)+=563; HPLC tR 9.6 minutes.

後処理

  1. customInto a 100 mL flask was placed
  2. temperatureThe reaction was heated to reflux
  3. temperatureAfter approximately 61 hours of refluxing
  4. customthe heat was removed
  5. additionTo the cooled mixture was added water/ice (50 mL)
  6. additionTo the aqueous mixture was added dichloromethane (50 mL)
  7. customtransferred to a separatory funnel
  8. extractionThe aqueous layer was extracted with dichloromethane (3×50 mL)
  9. washThe combined organics were washed with water
  10. dry with materialsaturated sodium chloride, and then dried over sodium sulfate
  11. filtrationThe dried organic solution was filtered
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customdried under high vacuum overnight
  14. customThe yellow foam was purified by Biotage chromatography (40+M cartridge; 0 to 5% methanol/dichloromethane over 25 CV)

出典と根拠

ORDレコード
ord-2cb29c6e192d4c319762145c3fd3b46a
出典データセット
uspto-grants-2015_08
特許番号
US09107956B2

反応ノート

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