Sodium hydride → Chloro-6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidine

HRID 2200786Notes

Reaction equation

[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[Cl:12][C:13]1[CH:18]=[C:17](Cl)[N:16]=[C:15]([C:20]([F:23])([F:22])[F:21])[N:14]=1.[H-].[Na+]>O1CCCC1>[Cl:12][C:13]1[CH:18]=[C:17]([O:11][CH:8]2[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)[N:16]=[C:15]([C:20]([F:22])([F:23])[F:21])[N:14]=1

Participants

Conditions

Temperature: 0 °C

Procedure

1,4-Dioxaspiro[4.5]decan-8-ol (3.64 g, 23.0 mmol, Acros Organics) and 4,6-dichloro-2-(trifluoromethyl)pyrimidine (5.00 g, 23.0 mmol SynChem, Inc.) were dissolved in tetrahydrofuran (41 mL) in a vial and cooled to 0° C. A 60% mixture of sodium hydride in oil (1.10 g, 27.5 mmol, Aldrich) was added. The reaction was stirred for 30 minutes at 0° C. and at 25° C. for 60 hours at which time TLC analysis showed that most of the starting material had been consumed. The reaction was quenched with water, and was extracted with ethyl acetate and the organic extracts were washed with water, saturated NaCl, dried (MgSO4) and stripped in vacuo. The product was purified by silica gel chromatography using 10-20% ethyl acetate (EtOAc)/hexanes to give the product 4-113 chloro-6-(1,4-dioxaspiro[4.5]dec-8-yloxy)-2-(trifluoromethyl)pyrimidine as a white solid (5.35 g). 1H NMR (400 MHz, CDCl3) δ: 6.90 (s, 1H), 5.35 (m, 1H), 3.95 (s, 4H), 1.60-2.05 (m, 8H).

Workup

customhad been consumed
customThe reaction was quenched with water
extractionwas extracted with ethyl acetate
washthe organic extracts were washed with water, saturated NaCl
dry with materialdried (MgSO4)
customThe product was purified by silica gel chromatography

Sources & evidence

ORD record: ord-846ed0ad1744470f9b1c6d6f8c1fa30f
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359358B2

Reaction notes

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