Sodium Carbonate → 4-[3-{6-[3-Acetyl-5-(2,2-difluoro-benzo[1,3]dioxol-5-yl)-phenoxy]hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

HRID 417043Notes

Reaction equation

HRID 417043 reaction equation
[CH2:1]([O:3][C:4](=[O:46])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26](OS(C(F)(F)F)(=O)=O)[CH:25]=[C:24]([C:36](=[O:38])[CH3:37])[CH:23]=2)[C:10]=1[CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH3:2].[F:47][C:48]1([F:60])[O:52][C:51]2[CH:53]=[CH:54][C:55](B(O)O)=[CH:56][C:50]=2[O:49]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.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>[CH2:1]([O:3][C:4](=[O:46])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([C:55]3[CH:54]=[CH:53][C:51]4[O:52][C:48]([F:60])([F:47])[O:49][C:50]=4[CH:56]=3)[CH:25]=[C:24]([C:36](=[O:38])[CH3:37])[CH:23]=2)[C:10]=1[CH2:39][CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 17750030(2,2-Difluoro-1,3-dioxaindan-5-yl)boronic acidHCID 594968454-[3-[6-(3-Acetyl-5-trifluoromethanesulfonyloxy-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

Product 1

HCID 594967934-[3-{6-[3-Acetyl-5-(2,2-difluoro-benzo[1,3]dioxol-5-yl)-phenoxy]hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl esterYield 59.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-[3-[6-(3-acetyl-5-trifluoromethanesulfonyloxy-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (500 mg) in 1,2-dimethoxyethane (5 mL) were added 2,2-difluoro-benzo[1,3]dioxole-5-boronic acid (273 mg), 2 M aq. sodium carbonate solution (1.0 mL) and Pd(PPh3)4 (8 mg) and the resulting mixture was stirred at 90° C. for 3 h. Then the reaction mixture was diluted with ethyl acetate, filtered through Celite and washed with water and brine. The organic extract was dried over anhydrous sodium sulfate, concentrated and purified on a silica gel column using ethyl acetate and hexanes to yield 300 mg of the title compound (59% yield). HRMS calcd for C38H44O9F2 [M+Na]+ 705.2845, observed 705.2843.

Workup

  1. filtrationfiltered through Celite
  2. washwashed with water and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. custompurified on a silica gel column

Sources & evidence

ORD record
ord-78c7c489e5ce409e8951e5b564b94cca
Source dataset
uspto-grants-2012_01
Patent number
US08088936B2

Reaction notes

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