Sodium hydride → (6S)-6-[(5-Bromo-2-thienyl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine

HRID 1446081Notes

Reaction equation

[H-].[Na+].[N+:3]([C:6]1[N:7]=[C:8]2[N:13]([CH:14]=1)[CH2:12][C@H:11]([OH:15])[CH2:10][O:9]2)([O-:5])=[O:4].[Br:16][C:17]1[S:18][C:19]([CH2:22]Br)=[CH:20][CH:21]=1>CN(C=O)C>[Br:16][C:17]1[S:18][C:19]([CH2:22][O:15][C@@H:11]2[CH2:10][O:9][C:8]3=[N:7][C:6]([N+:3]([O-:5])=[O:4])=[CH:14][N:13]3[CH2:12]2)=[CH:20][CH:21]=1

Participants

Conditions

Temperature: 0 °C

Procedure

NaH (60% w/w, 0.60 g, 15 mmol) was added to a solution of (6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-ol (2.00 g, 10.8 mmol) and 2-bromo-5-(bromomethyl)thiophene (prepared by the method of Mamane et al., Synthesis, 3; 2003; 455-467) (3.20 g, 12.5 mmol) in DMF (40 mL) at 0° C. The mixture was stirred at 0° C. for 2 h, then poured onto ice and extracted with EtOAc (2×200 mL). The organic layer was dried and evaporated. Column chromatography (hexanes/EtOAc, gradient elution) gave the titled compound (2.985 g, 77%) as a white solid. APCI MS m/z 360, 362 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 8.00 (s, 1H), 7.11 (d, J=3.7 Hz, 1H), 6.95 (d, J=3.7 Hz, 1H), 4.79 (d, J=13.2 Hz, 1H), 4.76 (d, J=13.2 Hz, 1H), 4.60 (dt, J=12.0, 1.6 Hz, 1H), 4.44 (d, J=12.0 Hz, 1H), 4.19-4.25 (m, 3H).

Workup

customprepared by the method of Mamane et al., Synthesis, 3
customat 0° C
additionpoured onto ice
extractionextracted with EtOAc (2×200 mL)
customThe organic layer was dried
customevaporated
washColumn chromatography (hexanes/EtOAc, gradient elution)

Sources & evidence

ORD record: ord-eaaa24c2da624cdeb4d9c67f7aa89a7e
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07666864B2

Reaction notes

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