Hydrochloric Acid → HCID 67467808, compound

HRID 1908046Notes

Reaction equation

HRID 1908046 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][C:9]([F:27])=[CH:10][CH:11]=2)[C:6]1=O)C.[ClH:32].[NH2:33][N:34](C)[C:35](=O)OC(C)(C)C>C(O)C>[ClH:32].[F:27][C:9]1[CH:10]=[CH:11][C:12]2[O:13][C:14]3([C:5]4[CH:4]=[N:33][N:34]([CH3:35])[C:6]=4[C:7]=2[CH:8]=1)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]3

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 37482801-Boc-1-methylhydrazineHCID 58550804HCID 58550804, compound

Product 1

HCID 67467808HCID 67467808, compoundYield 102.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of tert-butyl 3-(diethoxymethyl)-6-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (2.6 g, 6.0 mmol) in ethanol (20 mL) was added hydrochloric acid (22.5 mL of 4 M, 89.8 mmol) (4 M in dioxane). The reaction mixture was allowed to stir at 25° C. for 2 hours. The solvent was removed under vacuum, and the obtained solid was azeotroped with ethanol (3×30 mL). 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 (1.1 mL, 7.2 mmol). The solution was allowed to stir overnight. To the thick beige-white slurry that formed was added hydrochloric acid (7.5 mL of 4 M, 29.9 mmol) (4 M in dioxane). The mixture was heated at 60° C. to yield a clear yellow solution. After 1 hour at 60° C., a white thick slurry developed. The slurry was allowed to slowly cool to 25° C. over 4 hours, and solids were collected by vacuum filtration. The cake was rinsed with a 10% solution of ethanol in hexanes (2×). Residual solvents were further removed under reduced pressure providing 8-fluoro-1-methyl-spiro[chromeno[4,3-c]pyrazole-4,4′-piperidine]hydrochloride (1.9 g, 92%). 1H NMR (400 MHz, DMSO) δ 7.59 (dd, J=9.3, 2.8 Hz, 1H), 7.43 (s, 1H), 7.27-7.10 (m, 2H), 4.12 (s, 3H), 3.28-3.11 (m, 4H), 2.59 (s, 1H), 2.22-2.02 (m, 4H). ESI-MS m/z calc. 273.1. found 274.1 (M+1)+. Retention time 0.84 minutes (3 min run).

Workup

  1. customThe solvent was removed under vacuum
  2. customthe obtained solid was azeotroped with ethanol (3×30 mL)
  3. dissolutionThe resulting beige-white solid was fully dissolved in ethanol (21 mL) at 25° C.
  4. stirringto stir 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. over 4 hours
  10. filtrationsolids were collected by vacuum filtration
  11. washThe cake was rinsed with a 10% solution of ethanol in hexanes (2×)
  12. customResidual solvents were further removed under reduced pressure

Sources & evidence

ORD record
ord-8aef052855f542a7ad0a3b388896989c
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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