Hydrochloric Acid → HCID 67468326, compound

HRID 1908005Notes

Reaction equation

HRID 1908005 reaction equation
C(O[CH:4](OCC)[CH:5]1[C:14]2([CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]2)[O:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=O)C.[ClH:31].[NH2:32][N:33](C)[C:34](=O)OC(C)(C)C>>[ClH:31].[ClH:31].[CH3:34][N:33]1[C:6]2[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=3[O:13][C:14]3([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[C:5]=2[CH:4]=[N:32]1

Participants

4

Reactant 3

HCID 313Hydrochloric Acid2×HCID 37482801-Boc-1-methylhydrazineHCID 58550808HCID 58550808, compound

Product 1

HCID 67468326HCID 67468326, compoundYield 80%

Conditions

Temperature
25 °C

Procedure

To tert-butyl 3-(diethoxymethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (72 g, 160 mmol) was added hydrochloric acid (610 mL of 4.0 M, 2.5 mol). The reaction mixture was allowed to stir at 25° C. for 2 hours. Solvent was removed under vacuum, and the obtained solid was azeotroped with EtOH (3×700 mL). The resulting beige-white solid was dissolved in EtOH (685 mL) at 25° C. prior to the addition of tert-butyl N-amino-N-methyl-carbamate (29 mL, 200 mmol). The solution was allowed to stir at 25° C. overnight. To the thick beige-white slurry that formed was added hydrochloric acid (200 mL of 4.0 M, 800 mmol). The mixture was heated at 60° C. to yield a clear yellow solution. After 1 hour at 60° C., a thick white slurry developed. The slurry was allowed to slowly cool to 25° C., and solids were collected by vacuum filtration. The filter cake was rinsed with a 10% solution of EtOH in hexane (2×500 mL). The solid was placed in a vacuum oven overnight (20 mm Hg/45° C.). 1-Methyl-1H-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]dihydrochloride (42 g, 78%) was obtained as an off-white solid. ESI-MS m/z calc. 255.3. found 256.3 (M+1)+; Retention time: 1.30 minutes (3 min run). 1H NMR (400 MHz, MeOD) δ 7.82-7.76 (m, 1H), 7.61 (s, 1H), 7.40-7.34 (s, 1H), 7.22-7.14 (m, 2H), 4.19 (s, 3H), 3.52-3.42 (m, 2H), 3.41-3.33 (m, 2H), 2.39-2.07 (m, 4H).

Workup

  1. customSolvent was removed under vacuum
  2. customthe obtained solid was azeotroped with EtOH (3×700 mL)
  3. dissolutionThe resulting beige-white solid was dissolved in EtOH (685 mL) at 25° C.
  4. stirringto stir at 25° C. overnight
  5. customTo the thick beige-white slurry that formed
  6. temperatureThe mixture was heated at 60° C.
  7. customto yield a clear yellow solution
  8. waitAfter 1 hour at 60° C.
  9. temperatureto slowly cool to 25° C.
  10. filtrationsolids were collected by vacuum filtration
  11. washThe filter cake was rinsed with a 10% solution of EtOH in hexane (2×500 mL)
  12. customwas placed in a vacuum oven overnight (20 mm Hg/45° C.)

Sources & evidence

ORD record
ord-3f461dc298d24145962a0a34905d5a10
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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