Water → Ethyl [6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidin-4-yl]acetate

HRID 2200799Notes

Reaction equation

[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]=[C:14]([CH:22](C(OCC)=O)[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:13]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.O.[O-]CC.[Na+]>C(O)C.C(=O)(O)[O-]>[O:4]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[N:17]=[C:16]([C:18]([F:21])([F:19])[F:20])[N:15]=[C:14]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:13]=3)[CH2:7][CH2:6]2)[O:1][CH2:2][CH2:3]1

Participants

Conditions

Temperature: 75 °C

Procedure

Diethyl [6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidin-4-yl]malonate (4.60 g, 9.95 mmol), was dissolved in ethanol (46 mL). Water (18 μL, 1.0 mmol) and 21% Sodium ethoxide in ethanol (0.37 mL, 1.0 mmol) were added. The reaction mixture was stirred at 75° C. for 1 hour. HPLC & LCMS analysis showed 60% decarboxylation. The heating was continued for another 2 hours (reaction complete). The reaction was diluted with aqueous bicarbonate, and extracted with EtOAc. The EtOAc extract was washed with brine, then dried (Na2SO4), and evaporated in vacuo to 3.4 g oil (88% yield). LCMS, HPLC, & NMR showed it to be clean enough to proceed. 1H NMR (400 MHz, DMSO-D6): δ7.20 (s, 1H); 5.20 (m, 1H, OCH); 4.10 (q, 2H, OCH2); 3.89 (s, 2H, CH2); 3.85 (s, 4H, OCH2); 1.5-2.0 (m, 8H); 1.15 (t, 3H, CH3). HPLC showed it to have UVmax 222 & 252 nm.

Workup

waitThe heating was continued for another 2 hours
custom(reaction complete)
extractionextracted with EtOAc
extractionThe EtOAc extract
washwas washed with brine
dry with materialdried (Na2SO4)

Sources & evidence

ORD record: ord-7984d033772b41279c39062948adfa3a
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359358B2

Reaction notes

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