Hydrochloric Acid → Terphenyl scaffold, 18

HRID 25833Notes

Reaction equation

HRID 25833 reaction equation
[OH-].[Na+].[CH2:3]([C:10]1[CH:11]=[C:12]([C:33]2[CH:38]=[CH:37][C:36]([CH2:39]CC#N)=[CH:35][C:34]=2[CH2:43][CH:44]([CH3:46])[CH3:45])[CH:13]=[CH:14][C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([O:22]CC#N)=[C:18]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:17]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.C(Cl)Cl.CO.CC[O:55][C:56]([CH3:58])=[O:57].[CH3:59][C:60]([OH:62])=[O:61]>CO.C1COCC1.O1CCOCC1.[Cl-].[Na+].O>[CH2:3]([C:10]1[CH:11]=[C:12]([C:33]2[CH:38]=[CH:37][C:36]([CH2:39][CH2:58][C:56]([OH:55])=[O:57])=[CH:35][C:34]=2[CH2:43][CH:44]([CH3:46])[CH3:45])[CH:13]=[CH:14][C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:59][C:60]([OH:62])=[O:61])=[C:18]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:17]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 121347153-(3',3''-Dibenzyl-4''-(cyanomethoxy)-2-isobutyl-1,1':4',1''-terphenyl-4-yl)propanenitrileHCID 21226129Dichloromethane methanolHCID 22609514Ethyl acetate acetate

Product 1

HCID 10189152Terphenyl scaffold, 18Yield 11%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

5 ml (41.5 mmol, 178 eqv) of a 25% aq. NaOH-solution was added to a solution of 134.0 mg (233.1 μmol) 3-(3′,3″-Dibenzyl-4″-(cyanomethoxy)-2-isobutyl-1,1′:4′,1″-terphenyl-4-yl)propanenitrile (29) in 8 ml MeOH, 8 ml THF and 1 ml 1,4-dioxane. The resulting mixture was refluxed for 29 h and then cooled to 0° C. After adjusting the pH to 2 by adding 1 N aq. HCl-solution, which led to a white precipitate, brine was added and the mixture was extracted with THF. The comb. org. fractions were washed twice with brine, dried over MgSO4 and evaporated. Column chromatography (first CH2Cl2/MeOH (10+1), then EtOAc/HOAc (95+5)) yielded 16.2 mg (26.4 μmol, 11%) 1b as a white solid: Rf (CH2Cl2/MeOH (10+1)) 0.20; 1H NMR (500 MHz, d4-MeOH+d4-HOAc) δ 1.06 (d, 6H, J=6.62 Hz), 1.99 (m, 1H), 2.83 (d, 2H, J=7.25 Hz), 3.03 (t, 2H, J=7.57 Hz), 3.31 (t, 2H, J=7.57 Hz), 4.31 (s, 2H), 4.40 (s, 2H), 5.09 (s, 2H), 7.27 (m, 3H), 7.41 (d, 1H, J=2.21 Hz), 7.45-7.54 (m, 10H), 7.57-7.62 (m, 5H); 13C NMR (100 MHz, d4-MeOH+d4-HOAc) δ 20.86, 22.84, 30.58, 31.59, 31.61, 36.67, 39.95, 43.23, 92.03, 112.62, 126.74, 126.80, 126.87, 128.35, 129.28, 129.31, 129.32, 129.74, 130.13, 131.04, 131.14, 131.18, 131.39, 132.69, 135.83, 139.17, 140.21, 140.77, 141.26, 141.47, 142.30, 142.38, 142.94, 176.09, 176.14; LRMS (FAB) m/z 658 (16), 635 (19), 331 (16), 329 (38), 309 (15), 297 (13), 193 (10), 179 (14), 177 (100), 155 (48), 154 (14), 153 (26), 152 (23), 135 (52), 121 (18), 119 (100); HRMS (FAB) Calcd. for C41H40O5Na: 635.277345. Found: 635.277200.

Workup

  1. temperatureThe resulting mixture was refluxed for 29 h
  2. additionwas added
  3. extractionthe mixture was extracted with THF
  4. washfractions were washed twice with brine
  5. dry with materialdried over MgSO4
  6. customevaporated

Sources & evidence

ORD record
ord-d6aa9dbe828d49a58dd71230e3b74067
Source dataset
uspto-grants-2005_02
Patent number
US06858600B2

Reaction notes

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