3-Fluorophenylboronic acid → HCID 68424893, compound

HRID 73159Notes

Reaction equation

HRID 73159 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7](Br)=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([CH:13]1[CH2:18][CH2:17][CH:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].[F:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C.O.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>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:33]2[CH:32]=[CH:31][CH:30]=[C:29]([F:28])[CH:34]=2)=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([CH:13]1[CH2:18][CH2:17][CH:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4]

Participants

8

Reactant 2

HCID 27339863-Fluorophenylboronic acidHCID 577953645-Bromo-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 68424893HCID 68424893, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Procedure

A degassed solution of 5-Bromo-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (70 mg, 0.15 mmol) and 3-fluorophenyl boronic acid (32 mg, 0.23 mmol) in a mixture of DME (2.0 mL) and 2M aqueous Na2CO3 (1.0 mL) was treated with Pd(PPh3)4 (17.6 mg, 0.015 mmol). The reaction was heated at reflux for 18 h. The reaction mixture was diluted with ethyl acetate and water. The organic layer was separated, washed with brine, dried and concentrated to a residue that was purified by preparative chromatography using EtOAc:hexanes as eluent to provide 5-(3-Fluoro-phenyl)-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester as an oil contaminated with triphenylphosphine oxide that could not be removed (61.7 mg). 1H NMR (CDCl3, 400 MHz): 7.65 (dd, 3H), 7.53 (t, 2H), 7.43 (m, 5H), 7.32 (m, 1H), 7.1 (m, 1H), 7.02 (s, 1H), 4.56 (m, 1H), 3.82 (s, 3H), 3.40 (m, 1H), 2.14 (br s, 1H), 2.05-1.88 (m, 4H), 1.78 (m, 1H), 1.68-1.54 (m, 5H), 1.51-1.26 (m, 4H), 0.98 (m, 1H), 0.75 (d, 3H), 0.72-0.54 (m, 2H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 18 h
  3. customThe organic layer was separated
  4. washwashed with brine
  5. customdried
  6. concentrationconcentrated to a residue that
  7. customwas purified by preparative chromatography

Sources & evidence

ORD record
ord-12b0a0774cd34481b43b1e6668c4c58d
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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