Water → (6R,7aS)-6-Azido-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one

HRID 455256Notes

Reaction equation

[N-:1]=[N+:2]=[N-:3].[Na+].Br[C@@H:6]1[CH2:25][N:9]2[C:10](=[O:24])[N:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[CH2:12][C@@H:8]2[CH2:7]1.O>CN(C=O)C>[N:1]([C@H:6]1[CH2:25][N:9]2[C:10](=[O:24])[N:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[CH2:12][C@@H:8]2[CH2:7]1)=[N+:2]=[N-:3]

Participants

Conditions

Temperature: 70 °C

Procedure

Sodium azide (80 mg, 1.2 mmol) was added to a solution of (6S,7aS)-6-Bromo-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one (350 mg, 1.0 mmol) in anhydrous DMF (10 mL), the mixture was heated to 70° C. and stirred for 2 hours. The mixture was cooled and poured into water (30 mL), extracted with ethyl acetate (3×20 mL), the organic layers was combined and washed with water (2×20 mL), brine (20 mL), dried over anhydrous sodium sulphate, filtered and concentrated. The residue was purified by silica gel column chromatography (eluting with petroleum ether/ethyl acetate=10:1) to give 260 mg (83%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 7.59 (d, 2H, J=9.3 Hz), 7.19 (d, 2H, J=8.4 Hz), 4.33 (t, 1H, J=6.3 Hz), 4.13-3.98 (m, 3H), 3.75-3.72 (m, 1H), 3.15 (dd, 1H, J1=12.6 Hz, J2=2.1 Hz), 2.19 (dd, 1H, J1=13.2 Hz, J2=3.9 Hz), 1.73-1.63 (m, 1H).

Workup

temperatureThe mixture was cooled
extractionextracted with ethyl acetate (3×20 mL)
washwashed with water (2×20 mL), brine (20 mL)
dry with materialdried over anhydrous sodium sulphate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel column chromatography (eluting with petroleum ether/ethyl acetate=10:1)

Sources & evidence

ORD record: ord-a4375deee4874a60ad72e55e99fbf8d0
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497288B2

Reaction notes

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