Potassium Phosphate, Tribasic → [6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl ester

HRID 1644749Notes

Reaction equation

HRID 1644749 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13](OS(C(F)(F)F)(=O)=O)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:24])[CH:11]=2)[CH:6]=1.CC1(C)C(C)(C)OB([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)O1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:24])[CH:11]=2)[CH:6]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 162181494,4,5,5-Tetramethyl-2-(4-methylbenzyl)-1,3,2-dioxaborolaneHCID 59326772(6-Fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester

Product 1

HCID 59350825[6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl esterYield 74.9%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (6-fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester (220 mg, 0.578 mmol), 4,4,5,5-tetramethyl-2-(4-methyl-benzyl)-1,3,2-dioxaborolane (402 mg, 1.731 mmol), palladium(II) acetate (17 mg, 0.0757 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (53 mg, 0.129 mmol), potassium phosphate (246 mg, 1.159 mmol), toluene (5 mL) and water (0.5 mL) was heated at 110° C. for 2 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (100 mL) and washed with brine (25 mL). The organic phase was dried over MgSO4, filtered and concentrated. Silica gel chromatography (93:7 hexanes-ethyl acetate) gave 145.7 mg (74.9%) of [6-fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl ester as a colorless oil which solidified on standing. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.92 (dd, J=8.8, 6.2 Hz, 1 H), 7.75 (s, 1 H), 7.63 (dd, J=12.4, 2.1 Hz, 1 H), 7.33 (td, J=8.8, 2.1 Hz, 1 H), 7.03 (d, J=7.8 Hz, 2 H), 6.92 (d, J=7.8 Hz, 2 H), 4.40 (s, 2 H), 3.93 (s, 2 H), 3.64 (s, 3 H), 2.30 (s, 3 H), 2.21 (s, 3 H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with brine (25 mL)
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-47c9c7c664c8490496879a551bf61e7c
Source dataset
uspto-grants-2012_02
Patent number
US08124629B2

Reaction notes

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