Sodium Carbonate → (1-Fluorocyclopentyl)(hydroxy)acetonitrile

HRID 222580

Reaction equation

[FH:1].[O:2]1[C:4]2([CH2:8][CH2:7][CH2:6][CH2:5]2)[CH:3]1[C:9]#[N:10].C(=O)([O-])[O-].[Na+].[Na+]>N1C=CC=CC=1.ClCCl>[F:1][C:4]1([CH:3]([OH:2])[C:9]#[N:10])[CH2:8][CH2:7][CH2:6][CH2:5]1

Participants

Conditions

Temperature: 0 °C

Procedure

Anhydrous dichloromethane (3 mL) and a 70% w/w solution of hydrogen fluoride (2.68 mL, 20.44 mmol) in pyridine are mixed in a polyethylene bottle at 0° C. under a nitrogen atmosphere. A solution of 1-oxa-spiro[2.4]heptane-2-carbonitrile (3.30 g, 26.76 mmol) in anhydrous dichloromethane (3.2 mL) is added slowly. The reaction is stirred at 0° C. for 1 h and at room temperature for 1 h. The mixture is cooled at 0° C. and a saturated solution of sodium carbonate is added carefully. The aqueous layer is extracted with diethyl ether. The organic layers are combined, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and the solvent is removed. The residue is purified by chromatography in a 20 g silica gel cartridge eluting with hexane:diethyl ether (100:0 to 80:20) to obtain 1.7 g of desired compound as a colourless oil. 1H NMR (CDCl3) δ (ppm): 4.47 (d, 1H), 3.50 (bs, 1H), 2.12-1.67 (m, 8H).

Workup

temperatureThe mixture is cooled at 0° C.
extractionThe aqueous layer is extracted with diethyl ether
washwashed with water and brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
customthe solvent is removed
customThe residue is purified by chromatography in a 20 g silica gel cartridge
washeluting with hexane:diethyl ether (100:0 to 80:20)

Sources & evidence

ORD record: ord-4a95bf4964c24cd6be35cb541c2a2421
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207344B2

Linked notes

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