Water → N'-(2-chloro-phenyl)-N'-((1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl)-hydrazinecarboxylic acid tert-butyl ester

HRID 1437865Notes

Reaction equation

HRID 1437865 reaction equation
C(N(CC)CC)C.[CH3:8][C@:9]12[C:15]([CH3:17])([CH3:16])[C@H:12]([CH2:13][CH2:14]1)[CH:11]([C:18](Cl)=[O:19])[C:10]2=[O:21].[C:22]([O:26][C:27]([NH:29][NH:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[Cl:37])=[O:28])([CH3:25])([CH3:24])[CH3:23].O>ClCCl>[C:22]([O:26][C:27]([NH:29][N:30]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[Cl:37])[C:18]([CH:11]1[C:10](=[O:21])[C@@:9]2([CH3:8])[C:15]([CH3:17])([CH3:16])[C@@H:12]1[CH2:13][CH2:14]2)=[O:19])=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 57941306(1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride2×HCID 57941352tert-Butyl 2-(2-chlorophenyl)hydrazine-1-carboxylate2×

Product 1

HCID 57941453N'-(2-chloro-phenyl)-N'-((1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl)-hydrazinecarboxylic acid tert-butyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

Triethylamine (43 mL, 309 mmol) was added over 2-3 min to a cooled (0° C.) solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 23.2 g, 103.8 mmol) in dry dichloromethane (260 mL), yielding a heavy precipitate. Dichloromethane (25 mL) was added, followed by N′-(2-chloro-phenyl)-hydrazinecarboxylic acid tert-butyl ester (Intermediate 30; 19.36 g, 79.8 mmol) in one portion. Dichloromethane (35 mL) was added and the mixture was stirred at 0° C. for 5 min and then heated in an oil bath at 50° C. for 4 h. The mixture was poured into cold water (500 mL) and the layers were separated. The aqueous layer was extracted with dichloromethane (2×300 mL) and the combined organic layers were washed with brine (200 mL), dried (magnesium sulfate), filtered, evaporated, and purified by silica gel chromatography, eluting with 20-100% ethyl acetate/petroleum ether. Fractions homogeneous for the product were evaporated and dried under high vacuum to give N′-(2-chloro-phenyl)-N′-((1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl)-hydrazinecarboxylic acid tert-butyl ester (23.4 g, 70%) as a pale foam.

Workup

  1. customyielding a heavy precipitate
  2. temperatureheated in an oil bath at 50° C. for 4 h
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with dichloromethane (2×300 mL)
  5. washthe combined organic layers were washed with brine (200 mL)
  6. dry with materialdried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. custompurified by silica gel chromatography
  10. washeluting with 20-100% ethyl acetate/petroleum ether
  11. customFractions homogeneous for the product were evaporated
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-ffa6b28f08c040ddb922076fda71c186
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

Loading…