p-Toluenesulfonic acid → N'-(propan-2-yl)(tert-butoxy)carbohydrazide

HRID 624627Notes

Reaction equation

HRID 624627 reaction equation
[CH3:1][C:2](=[N:4][NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH3:3].[BH3-]C#N.[Na+].CC1C(Br)=C(O)C(Br)=CC=1C1(C2C=C(Br)C(O)=C(Br)C=2C)OS(=O)(=O)C2C=CC=CC1=2.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[Na+]>C1COCC1>[CH:2]([NH:4][NH:5][C:6]([O:8][C:9]([CH3:11])([CH3:10])[CH3:12])=[O:7])([CH3:3])[CH3:1]

Participants

7

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 6451Bromocresol GreenHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 11435207N'-(propan-2-ylidene)(tert-butoxy)carbohydrazide

Product 1

HCID 11217534N'-(propan-2-yl)(tert-butoxy)carbohydrazideYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Alternatively, tert-Butyl 2-(propan-2-ylidene)hydrazinecarboxylate 2 (0.51 g, 3.0 mmol) was dissolved in 20 mL of THF, treated with NaBH3CN (0.19 g, 3.0 mmol) and a few mg of bromocresol green, followed by a solution of p-toluenesulfonic acid (0.57 g, 3.0 mmol) in 1.5 mL of THF which was added dropwise over approximately 1 h to maintain the reaction pH between 3.5-5.0. After stirring at room temperature for an additional hour, the solvent was removed by rotary evaporation, and the residue was partitioned between EtOAc (30 mL) and brine. The organic phase was extracted with sat. NaHCO3, 20 mL and brine, evaporated to a residue and dissolved in 10 mL of ethanol. The ethanolic solution was treated with 3.6 mL of 1M NaOH solution (3.6 mmol) and left to stir at rt for 30 min. The solvent was removed by rotary evaporation and the residue was taken up into ethyl acetate and extracted with water. The organic layer was evaporated under reduced pressure and the residue was purified by column chromatography using 5% MeOH in DCM as eluent to collect tert-butyl 2-isopropylhydrazinecarboxylate 3 (0.4 g, 77% yield): mp=47-49° C.; Rf=0.44 (5% MeOH in DCM); 1H NMR 300 MHz (CDCl3) d 6.03 (s, N—H, 1H), 3.92 (s, N—H, 1H), 3.14 (m, 1H), 1.46 (s, 9H), 1.02 (d, 6H, J=6 Hz); 13C NMR 300 MHz (CDCl3) d 157.2, 80.8, 51.2, 28.7, 21.0.

Workup

  1. additionwas added dropwise over approximately 1 h
  2. temperatureto maintain the reaction pH between 3.5-5.0
  3. customthe solvent was removed by rotary evaporation
  4. customthe residue was partitioned between EtOAc (30 mL) and brine
  5. extractionThe organic phase was extracted with sat. NaHCO3, 20 mL and brine
  6. customevaporated to a residue
  7. dissolutiondissolved in 10 mL of ethanol
  8. waitleft
  9. stirringto stir at rt for 30 min
  10. customThe solvent was removed by rotary evaporation
  11. extractionextracted with water
  12. customThe organic layer was evaporated under reduced pressure
  13. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-7ba3ea200e694b48b7b90c8e31c063f1
Source dataset
uspto-grants-2016_04
Patent number
US09303043B2

Reaction notes

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