Hydrochloric Acid → 4-(Ethoxycarbonyl)-5,6-dihydro-2H-pyran-3-carboxylic acid

A mixture of acetic anhydride (5.19 g, 4.8 mL, 50.9 mmol), DIPEA (6.58 g, 8.89 mL, 50.9 mmol) and sodium formate (5.19 g, 76.3 mmol) was stirred at RT for 1 h. A solution of ethyl 5-(trifluoromethylsulfonyloxy)-3,6-dihydro-2H-pyran-4-carboxylate (8.6 g, 25.4 mmol; prepared according to WO2010038167) in DMF (50 mL) was added dropwise, followed by the addition of palladium (II) acetate (286 mg, 1.27 mmol) and LiCl (3.24 g, 76.3 mmol). After stirring at RT for 1.5 h the black suspension was poured on 2M aqueous HCl solution (100 mL) and EtOAc (100 mL) and the layers were separated. The aqueous layer was extracted twice with EtOAc (100 mL). The organic layers were washed twice with H2O and once with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 120 g column using an MPLC system eluting with a gradient of CH2Cl2:MeOH (100:0 to 80:20). Light brown oil (4.14 g; 81.3%). MS (ESI): m/z=199.06 [M−H]−.

1. stirringAfter stirring at RT for 1.5 h the black suspension
2. customthe layers were separated
3. extractionThe aqueous layer was extracted twice with EtOAc (100 mL)
4. washThe organic layers were washed twice with H2O and once with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. additiontreated with silica gel
8. customevaporated
9. customThe compound was purified by silica gel chromatography on a 120 g column
10. washeluting with a gradient of CH2Cl2:MeOH (100:0 to 80:20)

ORD record

ord-39b0ee966c2c473586d8fcbee814659e

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09353102B2