Toluene → HCID 57586550, compound

HRID 420408Notes

Reaction equation

HRID 420408 reaction equation
C1(C)C=CC=CC=1.Br[C:9]1[CH:10]=[C:11]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]2[C:32]([CH2:44][CH2:45][C:46]([OH:48])=[O:47])=[C:33]([CH:41]=[CH:42][CH:43]=2)[O:34][CH2:35][CH2:36][CH2:37][C:38]([OH:40])=[O:39])[CH:12]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([N:21]([CH3:23])[CH3:22])=[CH:17][CH:16]=2)[CH:14]=1.[F:49][C:50]1[CH:51]=[C:52](B(O)O)[CH:53]=[CH:54][CH:55]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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.O>[C:46]([CH2:45][CH2:44][C:32]1[C:31]([CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][O:24][C:11]2[CH:12]=[C:13]([C:15]3[CH:16]=[CH:17][C:18]([N:21]([CH3:22])[CH3:23])=[CH:19][CH:20]=3)[CH:14]=[C:9]([C:54]3[CH:53]=[CH:52][CH:51]=[C:50]([F:49])[CH:55]=3)[CH:10]=2)=[CH:43][CH:42]=[CH:41][C:33]=1[O:34][CH2:35][CH2:36][CH2:37][C:38]([OH:40])=[O:39])([OH:48])=[O:47]

Participants

7

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 27339863-Fluorophenylboronic acidHCID 57586441HCID 57586441, compound

Product 1

HCID 57586550HCID 57586550, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

In a reaction vessel charged with 4 mL of toluene and 1 mL of water, was added 45 mg (0.072 mmol) of 4-[3-[6-(5-bromo-4′-dimethylamino-biphenyl-3-yloxy)-hexyl]-2-(2-carboxy-ethyl)-phenoxy]-butyric acid, 3-fluorophenylboronic acid (20 mg, 0.144 mmol), and potassium phosphate (35.9 mg, 0.144 mmol). This mixture was put under an atmosphere of nitrogen and 4.16 mg of tetrakis(triphenylphosphine)palladium(0) was added. This mixture was stirred and was heated overnight at 90° C. At this time, analysis of an aliquot by LC-MS, indicated the formation of the desired product. To the reaction mixture was added 2N HCl to effect pH=˜6. The aqueous phase was thrice extracted with ethyl acetate. The combined organic phases were dried with MgSO4, filtered and washed with ethyl acetate. The filtrate was concentrated in vacuo to provide a solid which was purified by preparative HPLC to provide 46 mg of product. Example 57 was characterized by low resolution mass spectrometry where signals corresponding to the following were observed: ES(+)=598+Na, ES(−)=597. Example 57 was also characterized by high resolution mass spectrometry where signals corresponding to the following were observed: m/e calculated for C37H39FO6 598.273068; found compatible with (M+Na)1+=621.2624.

Sources & evidence

ORD record
ord-d5d3ee7025c24cbea2aac9d996edd8b5
Source dataset
uspto-grants-2012_01
Patent number
US08093385B2

Reaction notes

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