tert-butyl 3-oxotetrahydro-1H-oxazolo[3,4-a]pyrazine-7(3H)-carboxylate → (r)-Tert-butyl 3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

HRID 1487698Notes

Reaction equation

[Na].[OH:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=1.O=C1[N:14]2[CH2:15][CH2:16][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:18][CH:13]2[CH2:12]O1>CN(C=O)C>[N:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH2:12][C@@H:13]2[NH:14][CH2:15][CH2:16][N:17]([C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[CH2:18]2)[CH:4]=1

Participants

Conditions

Temperature: 120 °C

Procedure

3-Hydroxypyridine sodium salt (Acros, 7.23 g, 61.7 mmol) was added to a solution of tert-butyl tetrahydro-3-oxo-1H-oxazolo[3,4-a]pyrazine-7(3H)-carboxylate (5.00 g, 20.6 mmol) in DMF (50 mL). The reaction mixture was heated to 120° C. for 60 h. Upon cooling to rt, the reaction mixture was concentrated under reduced pressure. The material was dissolved in H2O (100 mL) and was extracted with EtOAc (3×150 mL). The combined organics were washed with 1 N NaOH (3×200 mL) and brine (200 mL), dried over dried over Na2SO4, filtered, and concentrated under reduced pressure. Recrystallization from EtOAc/Hexanes (1:4) gave 3.068 g (51%) of the desired product as an off-white solid.

Workup

temperatureUpon cooling to rt
concentrationthe reaction mixture was concentrated under reduced pressure
dissolutionThe material was dissolved in H2O (100 mL)
extractionwas extracted with EtOAc (3×150 mL)
washThe combined organics were washed with 1 N NaOH (3×200 mL) and brine (200 mL)
customdried
dry with materialover dried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customRecrystallization from EtOAc/Hexanes (1:4)

Sources & evidence

ORD record: ord-8c0970bda4ae49c4b32590b6650b6b88
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09428522B2

Reaction notes

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