3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(3H)-benzoxazolone synthesis

6synthesis methods

Product Name:3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(3H)-benzoxazolone
CAS Number:1220696-32-1
Molecular formula:C14H18BNO4
Molecular Weight:275.11

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3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(3H)-benzoxazolone

1220696-32-1
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Yield: 97%

Reaction Conditions:

with potassium acetate;palladium diacetate;XPhos for 3 h;Reflux;Inert atmosphere;Large scale;

Steps:

2.ii
A solution of 5-chloro-3-methyl-1,3-benzoxazol-2(3H)-one (stage ii)) (350 g, 1.91 mol), B₂pin₂(581.0 g, 2.29 mol) and KOAc (561.3 g, 5.72 mol) was vacuum degassed and purged with N₂(×3). Pd(OAc)₂(12.9 g, 57.2 mmol) and XPhos (54.6 g, 114 mmol) were added and the mixture was vacuum degassed and purged with N₂(×3). The mixture was heated to 75° C. A large exotherm was observed at 70° C. which warmed-up the mixture to reflux (100° C.). The reaction mixture was stirred for 1 h with no heating. HPLC analysis indicated 2.5% of the starting material remaining therefore the mixture was heated at 85° C. for 1 h. At this stage, no further change was observed. Additional portions of B₂pin₂(14.6 g, 57.2 mmol), KOAc (5.7 g, 57.2 mmol), Pd(OAc)₂(12.9 g, 57.2 mmol) and XPhos (27.3 g, 57.2 mmol) were added and the mixture was stirred for 1 h at 75° C. HPLC analysis showed no starting material remaining. The mixture was cooled to rt, filtered through a pad of Celite (501 g) and the cake was washed with EtOAc (2240 ml). The filtrate was combined with two other batches prepared in the same way (2×350 g) and evaporated. This gave 1865.1 g of the product as a grey solid (97% yield, 90.0% pure by LC, 82±2% pure by ¹H NMR (DMSO-d₆) assay vs TCNB). ¹H NMR (270 MHz, DMSO-d₆): δ 7.40-7.50 (m, 2H), 7.30 (d, 1H), 3.40 (s, 3H), 1.30 (s, 12H). LCMS (5 cm_ESCI_aq. formic acid_methanol_) t_R4.91 (min) m/z 276.1 (MH⁺).

References:

AstraZeneca AB;Lonn, Hans Roland;Connolly, Stephen;Swallow, Steven;Karlsson, Staffan PO;Aurell, Carl-Johan;Pontén, John Fritiof;Doyle, Kevin James;Van de Poël, Amanda Jane;Jones, Graham Peter;Watson, David Wyn;MacRitchie, Jaqueline Anne;Palmer, Nicholas John US9522894, 2016, B2 Location in patent:Page/Page column 53; 54

70672-82-1 Synthesis