Cesium fluoride → HCID 68733231, compound

HRID 1183591Notes

Reaction equation

HRID 1183591 reaction equation
[CH:1]1([CH2:4][O:5][C:6](=[O:25])[CH:7]([C:12]2[CH:17]=[C:16]([O:18][CH2:19][CH:20]3[CH2:22][CH2:21]3)[C:15](I)=[CH:14][C:13]=2[F:24])[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:2]1.[F:26][C:27]([F:38])([F:37])[C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.[F-].[Cs+].O.CCOC(C)=O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([CH2:4][O:5][C:6](=[O:25])[CH:7]([C:12]2[C:13]([F:24])=[CH:14][C:15]([C:31]3[CH:32]=[CH:33][C:28]([C:27]([F:38])([F:37])[F:26])=[CH:29][CH:30]=3)=[C:16]([O:18][CH2:19][CH:20]3[CH2:22][CH2:21]3)[CH:17]=2)[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 22728543Water ethylacetateHCID 68734023HCID 68734023, compound

Product 1

HCID 68733231HCID 68733231, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 2-(5-cyclopropylmethoxy-2-fluoro-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.2 g, 0.43 mmol) in anhydrous DME (10 mL) under argon was added 4-trifluoromethylphenylboronic acid (0.1 g, 0.53 mmol), CsF (0.16 g, 1.05 mmol), and Pd(PPh3)4 (0.015 g, 0.013 mmol). The reaction mixture was refluxed for 18 h, a water/EtOAc 15/15 mL mixture was added and the organic phase was separated and dried over MgSO4. The solvent was then evaporated to give a yellow oil which was purified by column chromatography over silica gel (Heptane-EtOAc gradient) to give 0.18 of 2-(2-cyclopropylmethoxy-5-fluoro-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a light yellow oil. 1H NMR (300 MHz, CDCl3/TMS): δ 7.70-7.64 (m, 4H), 7.05 (d, J=10.4 Hz, 1H), 7.01 (d, J=6.1 Hz, 1H), 4.09 (t, J=7.7 Hz, 1H), 4.02-3.87 (m, 2H), 3.78 (d, J=6.6 Hz, 2H), 2.04-1.90 (m, 1H), 1.74-1.65 (m, 1H), 1.60-1.45 (m, 1H), 1.25-1.05 (m, 2H), 0.95 (d, J=6.3 Hz, 6H), 0.60-0.40 (m, 4H), 0.30-0.10 (m, 4H). 13C NMR (75 MHz, CDCl3/TMS): δ 173.5, 154.3 (d, 1JCF=239.7 Hz), 151.9, 140.7, 132.0, 129.5, 126.6 (d, 2JCF=16.9 Hz), 124.8 (q, 3JCF=3.7 Hz), 124.0 (q, 1JCF=271.6 Hz), 117.0 (d, 2JCF=24.6 Hz), 113.6, 74.1, 69.6, 41.1, 41.5, 26.1, 22.7, 22.2, 10.2, 9.8, 3.2.

Workup

  1. temperatureThe reaction mixture was refluxed for 18 h
  2. customthe organic phase was separated
  3. dry with materialdried over MgSO4
  4. customThe solvent was then evaporated
  5. customto give a yellow oil which
  6. customwas purified by column chromatography over silica gel (Heptane-EtOAc gradient)

Sources & evidence

ORD record
ord-0b1af4d44029497981d82ef533e80083
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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