Diisopropylamine → HCID 20146597, compound

HRID 569910Notes

Reaction equation

HRID 569910 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH3:13][N:14]1[C:22]2[CH2:21][C:20]([CH3:24])([CH3:23])[CH2:19][C:18](=[O:25])[C:17]=2[CH:16]=[N:15]1.[CH:26](OCC)=[O:27]>CCCCCC.O1CCCC1.O>[CH3:13][N:14]1[C:22]2[CH2:21][C:20]([CH3:23])([CH3:24])[CH:19]([CH:26]=[O:27])[C:18](=[O:25])[C:17]=2[CH:16]=[N:15]1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 8025Ethyl formateHCID 13070778HCID 13070778, compoundHCID 178418339Butyllithium

Product 1

HCID 20146597HCID 20146597, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

n-Butyllithium (23.8 ml of a 2.60 M solution in hexane) was added slowly to an ice-cold solution of 8.7 ml of N,N-diisopropylamine in 30 ml of anhydrous tetrahydrofuran. The solution was stirred at 0° C. for 15 minutes and treated with 10.8 ml of hexamethylphosporamide; it was then stirred at 0° C. for 15 minutes and cooled to -78° C. A solution of 5 g of 1,5,6,7-tetrahydro-1,6,6-trimethyl-4H-indazol-4-one in 150 ml of anhydrous tetrahydrofuran was added dropwise, followed by the dropwise addition of 8.9 ml of ethyl formate. The reaction was allowed to warm to room temperature and was stirred for 20 hours and 150 ml of water was added and the mixture was extracted with dichloromethane. The aqueous layer was acidified with aqueous hydrochloric acid and extracted exhaustively with dichloromethane. The combined extracts were dried over magnesium sulfate and concentrated in vacuo to provide a dark oil which crystallized upon standing. Flash chromatography of this material (10% acetone in dichloromethane) on silica gel provided product as light yellow crystals. Recrystallization from hexane/toluene gave 4,5,6,7-tetrahydro-1,6,6-trimethyl-4-oxo-1 H-indazole-5-carboxaldehyde melting at about 131°-132° C.

Workup

  1. additiontreated with 10.8 ml of hexamethylphosporamide
  2. stirringit was then stirred at 0° C. for 15 minutes
  3. temperaturecooled to -78° C
  4. temperatureto warm to room temperature
  5. stirringwas stirred for 20 hours
  6. extractionthe mixture was extracted with dichloromethane
  7. extractionextracted exhaustively with dichloromethane
  8. dry with materialThe combined extracts were dried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customto provide a dark oil which
  11. customcrystallized
  12. customRecrystallization from hexane/toluene

Sources & evidence

ORD record
ord-b301c9f651914e8790f3f530dbe29170
Source dataset
uspto-grants-1988_03
Patent number
US04734430

Reaction notes

Loading…