Hydrochloric Acid → Spiro[cyclobutane-1,3'-indolin]-2'-one

HRID 74519

Reaction equation

HRID 74519 reaction equation
[C:1]1([N:7]([C:9]([CH:11]2[CH2:14][CH2:13][CH2:12]2)=[O:10])N)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Ca+2].[H-].[H][H].Cl.[OH-].[Na+]>CO.O>[NH:7]1[C:1]2[C:6](=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:11]2([CH2:14][CH2:13][CH2:12]2)[C:9]1=[O:10]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 3033859Calcium hydrideHCID 67337909N-phenylcyclobutanecarbohydrazideHCID 178418361HCID 178418361, compound

Product 1

HCID 13728292Spiro[cyclobutane-1,3'-indolin]-2'-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
230 °C

Procedure

Under a nitrogen atmosphere 1.50 g (7.89 mmol) cyclobutanecarboxylic acid N-phenylhydrazide and 530 mg (12.6 mmol) calcium hydride were mixed thoroughly and heated to 230° C. The mixture was stirred for 30 min at 230° C. and then cooled to RT again. The reaction mixture was carefully mixed with a solution of 7 mL water and 16 mL methanol. It was stirred for 1 h until no more hydrogen was released. Then the pH was adjusted to 1 with concentrated hydrochloric acid solution and the mixture was stirred for 1 h at 100° C. Using 4M sodium hydroxide solution the pH was adjusted to 3 and stirred overnight at RT. The precipitated substance was suction filtered and washed with 10 mL water. The mother liquor was evaporated down i.vac. and the residue was purified by preparative HPLC. The product fractions were combined, evaporated down i.vac. and dried.

Workup

  1. temperaturecooled to RT again
  2. stirringthe mixture was stirred for 1 h at 100° C
  3. stirringstirred overnight at RT
  4. filtrationfiltered
  5. washwashed with 10 mL water
  6. customThe mother liquor was evaporated down i.vac
  7. customand the residue was purified by preparative HPLC
  8. customevaporated down i.vac
  9. customand dried

Sources & evidence

ORD record
ord-7187c3dd5c874e0b9deb3e1aba52ef82
Source dataset
uspto-grants-2014_09
Patent number
US08829006B2

Linked notes

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