Hydrochloric Acid → Benzyl [(3aS,4R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydro-2H,3aH-cyclopenta[d][1,3]dioxol-4-yl]carbamate

HRID 1523230Notes

Reaction equation

HRID 1523230 reaction equation
C(OC(N[C@@H](CC1C=CC=CC=1)C([O-])=O)=O)(C)(C)C.[OH:20][C@@H:21]1[C@H:25]2[O:26][C:27]([CH3:30])([CH3:29])[O:28][C@H:24]2[C@H:23]([NH3+:31])[CH2:22]1.Cl.C(=O)([O-])[O-].[K+].[K+].Cl[C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41]>O.CC(CC(C)=O)C.C(OCC)(=O)C>[OH:20][C@@H:21]1[C@H:25]2[O:26][C:27]([CH3:29])([CH3:30])[O:28][C@H:24]2[C@H:23]([NH:31][C:40](=[O:41])[O:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:22]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 86718845HCID 86718845, compound

Product 1

HCID 12096654Benzyl [(3aS,4R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydro-2H,3aH-cyclopenta[d][1,3]dioxol-4-yl]carbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 7909Methyl Isobutyl KetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
30 °C

Procedure

To (3aS,4R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-aminium (2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate (10.06 g, 22.32 mmol) was added 30 mL ethyl acetate. The resulting thick slurry was put on ice-bath and stirred for 80 min. HCl (1 M, 24.5 mL, 24.5 mmol) was slowly added during 25 min while the temperature was kept below 5° C. (pH aqueous phase: 1-2). The phases were separated and the organic phase was washed with 10 mL of water after which the aqueous phases were combined. Potassium carbonate (10.3 g, 73.78 mmol) was dissolved in 25 mL of water. MIBK (30 mL) and benzyl chloroformate (4.17 g, 23.22 mmol) were added at 20° C. The combined aqueous phases were added slowly over 15 min and the mixture was warmed at 30° C. for 25 min without stirring. The phases were separated and the organic phase washed with 10 mL water. The organic phase was evaporated until about 11 g was remaining. Water (40 mL) was added and evaporation was continued until about 25 g was remaining. The mixture was filtered and the isolated product was washed with iso-octane and then dried at 40° C. in vacuum oven overnight. After drying, the title product was isolated (6.54 g), HPLC-purity: 97.7% (area), 1H-NMR assay: 100%.

Workup

  1. customThe resulting thick slurry was put on ice-bath
  2. customwas kept below 5° C.
  3. customThe phases were separated
  4. washthe organic phase was washed with 10 mL of water after which the aqueous phases
  5. additionThe combined aqueous phases were added slowly over 15 min
  6. stirringwithout stirring
  7. customThe phases were separated
  8. washthe organic phase washed with 10 mL water
  9. customThe organic phase was evaporated until about 11 g
  10. additionWater (40 mL) was added
  11. customevaporation
  12. filtrationThe mixture was filtered
  13. washthe isolated product was washed with iso-octane
  14. customdried at 40° C. in vacuum oven overnight
  15. customAfter drying

Sources & evidence

ORD record
ord-3f335e97ae584013bab7f5d1da7bf8b7
Source dataset
uspto-grants-2015_07
Patent number
US09079873B2

Reaction notes

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