Triphenylphosphine → 3-(1-BOC-2-(S)-azetidinylmethoxy)-5-bromo-6-methyl-pyridine

HRID 2305201Notes

Reaction equation

C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.[Br:32][C:33]1[C:34]([CH3:40])=[N:35][CH:36]=[C:37]([OH:39])[CH:38]=1.[C:41]([N:48]1[CH2:51][CH2:50][C@H:49]1[CH2:52]O)([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]>C1COCC1>[C:41]([N:48]1[CH2:51][CH2:50][C@H:49]1[CH2:52][O:39][C:37]1[CH:36]=[N:35][C:34]([CH3:40])=[C:33]([Br:32])[CH:38]=1)([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]

Participants

Conditions

Temperature: 0 °C

Procedure

Triphenylphosphine (6.3 g, 24 mmol) was dissolved in THF (100 mL), cooled to 0° C. and treated with diethylazodicarboxylate (3.8 mL, 24 mmol) for 15 min. Then the compound of 196d (3 g, 16 mmol) followed by 1-BOC-2-(S)-azetidinemethanol (3.4 g, 18 mmol) was added and the reaction was allowed to warm slowly to ambient temperature. After 3 days, the solvent was evaporated and the crude residue was chromatographed (silica gel; hexanes/ EtOAc, 4:1) to provide an oil. The product was contaminated with a byproduct related to the DEAD reagent and was taken forward as is; the subsequent allowed isolation of the byproduct and revealed ˜35 wt % contamination therefor the calculated yield was 70% (4.0 g, 11.2 mmol): TLC Rf 0.6 (1:1 hexanes/EtOAc); MS (CI/NH3) m/z 357 (M+H)+.

Workup

additionwas added
temperatureto warm slowly to ambient temperature
customthe solvent was evaporated
customthe crude residue was chromatographed (silica gel; hexanes/ EtOAc, 4:1)
customto provide an oil

Sources & evidence

ORD record: ord-d6300abd22084c4a8bdec060f19dda88
Source dataset: uspto-grants-2002_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06437138B1

Reaction notes

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