Hydrochloric Acid → trans-5,5-Difluorooctahydrocyclopenta[b][1,4]oxazine hydrochloride

HRID 81155Notes

Reaction equation

HRID 81155 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]2[CH2:14][CH2:15][C:16]([F:18])([F:17])[C@@H:9]12)C1C=CC=CC=1.[ClH:19]>CO>[ClH:19].[F:18][C:16]1([F:17])[C@@H:9]2[C@H:10]([O:11][CH2:12][CH2:13][NH:8]2)[CH2:14][CH2:15]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86724509trans-4-Benzyl-5,5-difluorooctahydrocyclopenta[b][1,4]oxazine

Product 1

HCID 86724510trans-5,5-Difluorooctahydrocyclopenta[b][1,4]oxazine hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Trans-4-benzyl-5,5-difluorooctahydrocyclopenta[b][1,4]oxazine (350 mg, 1.38 mmol) was dissolved in MeOH (10 mL). 3M HCl in MeOH (1.5 mL) was added and the solution was stirred for 1 hour. The solvent was evaporated and further azeotroped using toluene. The residue was then dissolved in MeOH (10 mL), and 20% Pd(OH)2/C (20% by wt, 50 mg) added. Hydrogen was purged through the reaction for 10 minutes and stirring was continued at room temperature under 1 atm of hydrogen for 16 hours. The reaction was filtered through celite, and the filtrate was concentrated to afford trans-5,5-difluorooctahydrocyclopenta[b][1,4]oxazine hydrochloride. 1H NMR (400 MHz, CD3OD) δ 4.16 (dd, J=13.6, 4.0 Hz, 1H), 3.78-3.92 (m, 2H), 3.65 (m, 1H), 3.43 (dd, J=13.2, 2.4 Hz, 1H), 3.28-3.31 (m, 2H), 2.15-2.55 (m, 2H), 1.89 (m, 1H). MS ESI calc'd. for C7H11F2NO [M+H]+ 164. found 164.

Workup

  1. customThe solvent was evaporated
  2. customfurther azeotroped
  3. dissolutionThe residue was then dissolved in MeOH (10 mL)
  4. addition20% Pd(OH)2/C (20% by wt, 50 mg) added
  5. customHydrogen was purged through the reaction for 10 minutes
  6. stirringstirring
  7. waitwas continued at room temperature under 1 atm of hydrogen for 16 hours
  8. filtrationThe reaction was filtered through celite
  9. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-f0e3cb34f3ed45119a626529d2432854
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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