Water → HCID 89590878, compound

HRID 522353Notes

Reaction equation

Cl.[F:2][C:3]1([F:9])[CH2:8][CH2:7][CH2:6][NH:5][CH2:4]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:17][CH2:18][CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].O>CN(C=O)C.C(OCC)(=O)C>[Si:21]([O:20][CH2:19][CH2:18][CH2:17][N:5]1[CH2:6][CH2:7][CH2:8][C:3]([F:9])([F:2])[CH2:4]1)([C:24]([CH3:25])([CH3:26])[CH3:27])([CH3:23])[CH3:22]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 3,3-difluoropiperidine hydrochloride (518 mg) in DMF (15 mL) was added cesium carbonate (3.21 g) and (3-bromopropoxy)-tert-butyldimethylsilane (0.838 mL). The resulting reaction mixture was heated to 50° C. for 1.5 hours before cooling back to room temperature. Water and ethyl acetate were added to the reaction mixture. The mixture was extracted with ethyl acetate (2×). The combined organics were washed with water (2×), brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (ISCO, 0 to 40% ethyl acetate in hexanes with 1% triethylamine) gave the desired product (612 mg). 1H NMR (400 MHz, CDCl3): δ (ppm) 4.20 (t, 1H), 3.71-3.64 (m, 2H), 3.46 (t, 1H), 2.62 (t, 1H), 2.50-2.47 (m, 1H), 2.44-2.42 (m, 1H), 2.05-1.98 (m, 1H), 1.91-1.82 (m, 2H), 1.77-1.67 (m, 4H), 0.89 (d, 9H), 0.05 (s, 3H), 0.04 (s, 3H).

Workup

customThe resulting reaction mixture
temperaturebefore cooling back to room temperature
extractionThe mixture was extracted with ethyl acetate (2×)
washThe combined organics were washed with water (2×), brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by flash chromatography (ISCO, 0 to 40% ethyl acetate in hexanes with 1% triethylamine)

Sources & evidence

ORD record: ord-24af9d37e83f4c3aa8e7283f75d8c729
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328138B2

Reaction notes

Loading…