Toluene → HCID 86718845, compound

HRID 1523229Notes

Reaction equation

HRID 1523229 reaction equation
[NH2:1][C@H:2]1[C@@H:6]2[O:7][C:8]([CH3:11])([CH3:10])[O:9][C@@H:5]2[C@@H:4]([OH:12])[CH2:3]1.C1(C)C=CC=CC=1.[C:20]([O:24][C:25]([NH:27][C@H:28]([C:36]([OH:38])=[O:37])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>C(O)(C)C>[C:20]([O:24][C:25]([NH:27][C@@H:28]([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:36]([O-:38])=[O:37])=[O:26])([CH3:23])([CH3:21])[CH3:22].[OH:12][C@@H:4]1[C@H:5]2[O:9][C:8]([CH3:10])([CH3:11])[O:7][C@H:6]2[C@H:2]([NH3+:1])[CH2:3]1

Participants

5

Reactant 3

HCID 1140TolueneHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 10352168(3aR,4S,6R,6aS)-6-amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol

Product 1

HCID 86718845HCID 86718845, compoundYield 43.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Conditions

Temperature
66 °C

Procedure

(3aR,4S,6R,6aS)-6-Amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (80.0 g, 96%, 443.4 mmol), toluene (46.9 mL) and iso-propanol (500 mL) were taken to a flask with a stirrer. The mixture was heated, with stirring, to 31° C. when N-(tert-butoxycarbonyl)-L-phenylalanine (124.8 g, 99%, 465.5 mmol) was added together with iso-propanol (99 mL). The mixture was further heated to 66° C. when a clear solution was obtained. The solution was cooled and crystallization started at 55° C. The slurry was further cooled to ambient temperature and stirred overnight. The next day the slurry was cooled to 0° C. and stirred at this temperature for 120 min. The crystals were isolated on a glass filter, washed with cooled iso-propanol (500 mL) and dried in vacuum at 40° C. to give an amount of 85.8 g. The assay by titration was 99.0% and ee by LC 99.2%. The yield was 43.3%.

Workup

  1. temperatureThe mixture was heated
  2. customwas obtained
  3. temperatureThe solution was cooled
  4. customcrystallization
  5. customstarted at 55° C
  6. temperatureThe slurry was further cooled to ambient temperature
  7. temperatureThe next day the slurry was cooled to 0° C.
  8. stirringstirred at this temperature for 120 min
  9. customThe crystals were isolated on a glass
  10. filtrationfilter
  11. washwashed with cooled iso-propanol (500 mL)
  12. customdried in vacuum at 40° C.
  13. customto give an amount of 85.8 g

Sources & evidence

ORD record
ord-e9a86054c3d64b2da82c31cb20d9b78d
Source dataset
uspto-grants-2015_07
Patent number
US09079873B2

Reaction notes

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