Water → 6-(2-Hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

HRID 1640734Notes

Reaction equation

[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H](C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)C)[CH2:6][CH2:5]1.BrC1C=CC(=O)N(C(F)F)C=1.C([O-])([O-])=O.[Cs+].[Cs+].O>O1CCOCC1>[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[NH:7][CH2:6][CH2:5]1

Participants

Conditions

Temperature: 110 °C

Procedure

A microwave vial equipped with a flea stirbar was charged with (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan -2-yl)phenyl)ethyl)-1,3-oxazinan-2-one (20 mg, 0.047 mmol), 5-bromo-1-(difluoromethyl)pyridin-2(1H)-one (25 mg, 0.113 mmol), Cs2CO3 (27 mg, 0.083 mmol), H2O (0.1 mL) and dry dioxane (1 mL). The mixture was sparged with N2 for 10 min and heated at 110° C. in the microwave for 0.5 h. The mixture was diluted with glacial HOAc (0.1 mL) and MeOH (0.5 mL) and filtered. The filtrate was directly purified by prep HPLC to afford (S)-3-(S)-1-(4-(1-(difluoromethyl)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (11.8 mg, 57%) as an oil. LC-MS Method 1 tR=1.55 min, m/z=497, 248; 1H NMR (CDCl3) 1.13 (s, 3H), 1.19 (s, 3H), 1.56 (d, 3H), 2.15-2.35 (s, 4H), 2.42 (m, 2H), 2.88 (m, 1H), 5.71 (q, 1H), 6.64 (d, 1H), 7.04 (d, 2H), 7.18 (d, 2H), 7.30-7.40 (5H), 7.52 (1H), 7.60 (m, 1H), 7.75 (t, 1H).

Workup

customA microwave vial equipped with a flea stirbar
customThe mixture was sparged with N2 for 10 min
additionThe mixture was diluted with glacial HOAc (0.1 mL) and MeOH (0.5 mL)
filtrationfiltered
customThe filtrate was directly purified by prep HPLC

Sources & evidence

ORD record: ord-38f845638f124b24a1a5a8b4b3279c18
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08114868B2

Reaction notes

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