tert-Butyl 2-{[4-(pyridin-2-yl)phenyl]methyl}hydrazine-1-carboxylate → N'-(3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butyl)-N'-(4-pyridin-2-yl-benzyl)-hydrazinecarboxylic acid tert-butyl ester

HRID 1909352Notes

Reaction equation

HRID 1909352 reaction equation
[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]

Participants

4

Reactant 2

HCID 9796325tert-Butyl 2-{[4-(pyridin-2-yl)phenyl]methyl}hydrazine-1-carboxylateHCID 9903372(2S,3S)-(-)-3-tert-Butoxycarbonylamino-1,2-epoxy-4-phenylbutane

Product 1

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

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

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; 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.

Workup

  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)

Sources & evidence

ORD record
ord-9e3400b873c34fe19e2dde95ffb076b7
Source dataset
uspto-grants-2013_12
Patent number
US08598364B2

Reaction notes

Loading…