Formic Acid → (1RS,2SR,6RS,7SR,8RS)-8-(3-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02,6]decane-3,5-dione

HRID 407858Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](I)[CH:3]=1.N1CCCCC1.[CH3:15][C:16]1[CH:21]=[C:20]([CH3:22])[CH:19]=[C:18]([CH3:23])[C:17]=1[CH:24]1[C:32](=[O:33])[CH:31]2[CH:26]([CH:27]3[O:34][CH:30]2[CH:29]=[CH:28]3)[C:25]1=[O:35].C(O)=O>CN(C)C=O.ClCCl.O>[F:1][C:2]1[CH:3]=[C:4]([CH:29]2[CH2:28][CH:27]3[O:34][CH:30]2[CH:31]2[CH:26]3[C:25](=[O:35])[CH:24]([C:17]3[C:18]([CH3:23])=[CH:19][C:20]([CH3:22])=[CH:21][C:16]=3[CH3:15])[C:32]2=[O:33])[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Bis(triphenylphosphine)palladium diacetate (20 mg, 0.024 mmol), 1-fluoro-3-iodo-benzene (104 mg, 0.47 mmol) and piperidine (0.16 ml, 1.6 mmol) are added to a solution of (1RS,2SR,6RS,7SR)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.02,6]dec-8-en-3,5-dione (0.20 g, 0.71 mmol) in dry N,N-dimethylformamide (2 ml). Formic acid (0.06 ml, 1.6 mmol) is added and the reaction mixture is heated at 50° C. for 2 hours. The reaction mixture is cooled to room temperature, water (1 ml) and dichloromethane (1 ml) are added, and the mixture is stirred for 1 hour. The two phases are separated, the organic phase collected and the solvent is evaporated. The residue is purified by preparative reverse-phase HPLC to give (1RS,2SR,6RS,7SR,8RS)-8-(3-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02,6]decane-3,5-dione.

Workup

temperatureThe reaction mixture is cooled to room temperature
customThe two phases are separated
customthe organic phase collected
customthe solvent is evaporated
customThe residue is purified by preparative reverse-phase HPLC

Sources & evidence

ORD record: ord-4394443872004514b123596c6f130ee9
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754242B2

Reaction notes

Loading…