Hydrochloric Acid → HCID 67468652, compound

HRID 2204139Notes

Reaction equation

HRID 2204139 reaction equation
C(O/[CH:4]=[C:5]1\[C:6](=O)[C:7]2[C:12]([O:13][C:14]3\1[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]3)=[CH:11][C:10]([F:27])=[CH:9][CH:8]=2)C.[ClH:29].[NH2:30][N:31](C)[C:32](=O)OC(C)(C)C.O1CCOCC1>>[ClH:29].[ClH:29].[F:27][C:10]1[CH:9]=[CH:8][C:7]2[C:6]3[N:31]([CH3:32])[N:30]=[CH:4][C:5]=3[C:14]3([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3)[O:13][C:12]=2[CH:11]=1

Participants

5

Reactant 4

HCID 313Hydrochloric Acid2×HCID 312751,4-DioxaneHCID 37482801-Boc-1-methylhydrazineHCID 58550799HCID 58550799, compound

Product 1

HCID 67468652HCID 67468652, compoundYield 68.5%

Conditions

Temperature
25 °C

Procedure

To tert-butyl (3Z)-3-(ethoxymethylene)-7-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (2.6 g, 5.9 mmol) was added hydrochloric acid (22.3 mL, 89.1 mmol) (4 M in dioxane). The reaction mixture was allowed to stir at 25° C. for 2 hours. Solvent was removed under vacuum, and the obtained solid was dissolved in EtOH (3×25 mL) and the solvent was evaporated to dryness. The resulting beige-white solid was fully dissolved in ethanol (21 mL) at 25° C. prior to the addition of tert-butyl N-amino-N-methyl-carbamate (1.0 g, 7.1 mmol). The solution was allowed to stir at 25° C. overnight. To the thick beige-white slurry that formed was added hydrochloric acid, 4 M in dioxane (7.4 mL, 29.7 mmol). The mixture was heated at 60° C. to yield a clear yellow solution. After 1 hour at 60° C., a thick beige-white slurry developed. The slurry was allowed to slowly cool to 25° C. over 1 hour, and solids were collected by vacuum filtration. The cake was rinsed with a 10% solution of ethanol in hexanes (2×). Residual solvent was further removed under reduced pressure providing 7-fluoro-1-methyl-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine] dihydrochloride (1.4 g, 67%) as a light tan solid. ESI-MS m/z calc. 273.1, found 274.3 (M+1)+; Retention time: 1.59 minutes (3 min run). 1H NMR (400 MHz, MeOD) δ 7.80 (dd, J=8.7, 6.1 Hz, 1H), 7.45 (d, J=1.7 Hz, 1H), 7.00 (dd, J=9.8, 2.6 Hz, 1H), 6.91 (td, J=8.6, 2.6 Hz, 1H), 4.14 (s, 3H), 3.53-3.42 (m, 2H), 3.41-3.33 (m, 2H), 2.29 (d, J=13.9 Hz, 2H), 2.23-2.11 (m, 2H).

Workup

  1. customSolvent was removed under vacuum
  2. dissolutionthe obtained solid was dissolved in EtOH (3×25 mL)
  3. customthe solvent was evaporated to dryness
  4. dissolutionThe resulting beige-white solid was fully dissolved in ethanol (21 mL) at 25° C.
  5. stirringto stir at 25° C. overnight
  6. customTo the thick beige-white slurry that formed
  7. temperatureThe mixture was heated at 60° C.
  8. customto yield a clear yellow solution
  9. waitAfter 1 hour at 60° C.
  10. temperatureto slowly cool to 25° C. over 1 hour
  11. filtrationsolids were collected by vacuum filtration
  12. washThe cake was rinsed with a 10% solution of ethanol in hexanes (2×)
  13. customResidual solvent was further removed under reduced pressure

Sources & evidence

ORD record
ord-a73151faecfc4517991c44305f7b1f49
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

Loading…