Sodium Bicarbonate → (R)-5-(5-(3,6-dihydro-2H-pyran-4-yl)-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one

温度

110 °C

A solution of (R)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one (intermediate B6.1) (151 mg, 412 μmol) and 4-methyl-N′-(2H-pyran-4(3H,5H,6H)-ylidene)benzenesulfonohydrazide (CAS1240042-12-9) (122 mg, 454 μmol) in dioxane (5 ml) was treated under argon with 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-PHOS) (19.7 mg, 41.2 μmol), bis(dibenzylideneacetone) palladium (11.9 mg, 20.6 μmol) and finally lithium tert-butoxide (72.6 mg, 907 μmol). The reaction mixture was stirred in a sealed microwave tube at 110° C. for 16 hours. For the workup, the reaction mixture was poured on a saturated solution of sodium hydrogencarbonate followed by 2 extractions with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulphate, filtered and evaporated at reduced pressure to give brown oil. The residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 20:80 as the eluent. The (R)-5-(5-(3,6-dihydro-2H-pyran-4-yl)-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one (76 mg, 50% yield) was obtained as an off-white foam. MS (ISP): m/z=370.2 [M+H]+.

1. extractionfollowed by 2 extractions with ethyl acetate
2. washThe combined organic layers were washed with brine
3. dry with materialdried over sodium sulphate
4. filtrationfiltered
5. customevaporated at reduced pressure
6. customto give brown oil
7. customThe residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 20:80 as the eluent

ORDレコード

ord-b968e67a63a442f4ba55a97bccde5267

出典データセット

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08877744B2