1-Chloroethyl chloroformate → 1'-isopropyl-1'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-one

HRID 536289Notes

Reaction equation

HRID 536289 reaction equation
C([N:8]1[CH2:25][CH2:24][C:11]2([O:19][C:18]3[CH:17]=[N:16][N:15]([CH:20]([CH3:22])[CH3:21])[C:14]=3[C:13](=[O:23])[CH2:12]2)[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClCCCl>[CH:20]([N:15]1[C:14]2[C:13](=[O:23])[CH2:12][C:11]3([CH2:10][CH2:9][NH:8][CH2:25][CH2:24]3)[O:19][C:18]=2[CH:17]=[N:16]1)([CH3:22])[CH3:21]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 680661841-benzyl-1'-isopropyl-1'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-one

Product 1

HCID 668369941'-isopropyl-1'H-spiro[piperidine-4,5'-pyrano[3,2-c]pyrazol]-7'(6'H)-oneYield 86%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-Benzyl-1′-isopropyl-1′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-7′(6′H)-one (81 mg, 0.22 mmol) was dissolved in 10 mL 1,2-dichloroethane. Added 1-chloroethyl chloroformate (60 mL, 0.54 mmol) was added and the mixture was stirred 1 h at reflux then cooled to room temperature. The volatiles were removed under reduced pressure and the residue taken up in 10 mL methanol and heated at reflux for 1 h. The mixture was cooled to ambient temperature and the volatiles were removed under reduced pressure. The residue was taken up in 50 mL saturated aqueous sodium bicarbonate and extracted 2×30 mL ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered and concentrated to yield 46 mg (86%) of 1′-isopropyl-1′H-spiro[piperidine-4,5′-pyrano[3,2-c]pyrazol]-7′(6′H)-one as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 7.20 (s, 1H), 5.13 (spt, 1H), 2.93 (m, 2H), 2.80 (dt, J=12.8, 4.0 Hz, 2H), 2.64 (s, 2H), 2.02 (m, 2H), 1.63 (m, 2H), 1.40 (m, 6H); m/z (M+1)=250.2

Workup

  1. temperatureat reflux
  2. customThe volatiles were removed under reduced pressure
  3. temperatureheated
  4. temperatureat reflux for 1 h
  5. temperatureThe mixture was cooled to ambient temperature
  6. customthe volatiles were removed under reduced pressure
  7. extractionextracted 2×30 mL ethyl acetate
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-391c138e646b473fb28a69ec5d0946e7
Source dataset
uspto-grants-2014_10
Patent number
US08859577B2

Reaction notes

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