6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-carboxylic acid synthesis

Yield:1173003-61-6 98%

Reaction Conditions:

Stage #1: 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-carboxylic acid ethyl esterwith water;lithium hydroxide in tetrahydrofuran;ethanol at 60; for 48 h;
Stage #2: with hydrogenchloride in water; pH=2;

Steps:

6,7-Dihydro-5H-pyrazolo[5,l-￡] [l,3]oxazine-3-carboxylic acid[00360] A solution of 6,7-dihydro-5H-pyrazolo[5,l-6][l ,3]oxazine-3-carboxylic acid ethyl ester(9.67 g, 49.3 mmol) in tetrahydrofuran (150 mL), ethanol (50 mL) and IM of lithium hydroxide in water (148 mL, 148 mmol) was stirred at 60 ⁰C for 2 days. After cooling, the volatiles were removed. The residue was transferred to an Erlenmeyer flask and ice was added. The reaction was acidified to pH 2 with 1OM HCl. The aqueous layer was extracted several times with 3/1 chloroform/IPA. The combined organic layerss were dried (Na₂SO₄), filtered, concentrated to afford the acid as a solid (8.14 g, 98%). ¹H NMR (400MHz, DMSO-40 ￡7.57 (s, IH), 4.37 (t, 2H, J= 5.29 Hz), 4.07 (t, 2H, J= 6.11 Hz), 2.20-2.15 (m, 2H).

References:

WO2009/89057,2009,A1 Location in patent:Page/Page column 56-57