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4-Iodophenol → 3-(4-(Carboxymethoxy)-2,2''-diisobutyl-3-naphthalen-1-ylmethyl-[1,1':4',1'']-terphenyl-4''-yl)propionic acid

HRID 25848
Notes
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Reaction equation

HRID 25848 reaction equation
[Cl-].[Na+].O.O.Br[C:6]1[CH:7]=[CH:8][C:9]([OH:20])=[C:10]([C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=O)[CH:11]=1.C(C1C=C(C2C=CC(CCC#N)=CC=2CC(C)C)C=CC=1C1C=CC(OCC#N)=C(CC2C=CC=CC=2)C=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(C1C=C([C:86]2[CH:91]=[CH:90][C:89](CCC#N)=[CH:88][C:87]=2CC(C)C)C=CC=1OS(C(F)(F)F)(=O)=O)C1C=CC=CC=1.COC1C=CC=[CH:107][C:103]=1[C:104]([OH:106])=[O:105].C(C1C=C(C2C=CC(CCC#N)=CC=2[CH2:136][CH:137]([CH3:139])[CH3:138])C=CC=1OC)C1C=CC=CC=1.C(COC1C=CC(C2C=CC(C3C=CC(CCC#N)=CC=3CC(C)C)=CC=2CC2C3C(=CC=CC=3)C=CC=2)=CC=1[CH2:181][CH:182]([CH3:184])[CH3:183])#N.C(C1C=C(C2C=CC(CCC(O)=O)=CC=2CC(C)C)C=CC=1C1C=CC(O[CH2:205][C:206]([OH:208])=[O:207])=C(CC(C)C)C=1)C1C=CC=CC=1.I[C:229]1[CH:234]=CC(O)=[CH:231][CH:230]=1>CC(O)=O>[C:206]([CH2:205][O:20][C:9]1[CH:8]=[CH:7][C:6]([C:86]2[CH:87]=[CH:88][C:89]([C:27]3[CH:26]=[CH:25][C:24]([CH2:107][CH2:103][C:104]([OH:106])=[O:105])=[CH:23][C:22]=3[CH2:184][CH:182]([CH3:181])[CH3:183])=[CH:90][CH:91]=2)=[C:11]([CH2:139][CH:137]([CH3:136])[CH3:138])[C:10]=1[CH2:12][C:14]1[C:19]2[C:18](=[CH:234][CH:229]=[CH:230][CH:231]=2)[CH:17]=[CH:16][CH:15]=1)([OH:208])=[O:207]
ParticipantsProcedureSources & evidenceReaction notes

Participants

11

Reactant 9

HCID 108944-IodophenolHCID 113702-Methoxybenzoic acidHCID 2290095-Bromo-2-hydroxybenzophenoneHCID 10120948Terphenyl scaffold, 16HCID 121347103-(3'-Benzyl-2-isobutyl-4'-methoxy-1,1'-biphenyl-4-yl)propanenitrile2×
HCID 12134712
Trifluoro-methanesulfonic acid 3-benzyl-4'-(2-Cyano-ethyl)-2'-isobutyl-biphenyl-4-yl ester
HCID 121347153-(3',3''-Dibenzyl-4''-(cyanomethoxy)-2-isobutyl-1,1':4',1''-terphenyl-4-yl)propanenitrile
HCID 225652383-(4-Cyanomethoxy-3,2''-diisobutyl-2'-naphthalen-1-ylmethyl-[1,1':4',1'']-terphenyl-4''-yl)propionitrile
HCID 23713072Sodium chloride dihydrate

Product 1

HCID 225652143-(4-(Carboxymethoxy)-2,2''-diisobutyl-3-naphthalen-1-ylmethyl-[1,1':4',1'']-terphenyl-4''-yl)propionic acid

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 36.3 mg (55.26 μmol) 3-(2′,2″-Diisobutyl-4-methoxycarbonylmethoxy-3-naphthalen-1-ylmethyl-[1,1′:4′,1″]-terphenyl-4″-yl)propionic acid methyl ester (79) in 8 ml 1.4-dioxane 2.0 ml (16.60 mmol, 301 eq.) 25% aq. NaOH-solution and 2.0 ml (3.08 mmol, 56 eq.) 40% aq. solution of Bu4NOH were added. The resulting mixture was refluxed for 24 h and then cooled to 0° C. Acidification to pH 1 by adding 1 N aq. HCl-solution led to a white precipitate which was obtained by filtration. A filtration over silica gel with EtOAc/HOAc (95+5)) as an eluent and a following lyophilization of the obtained oily product from a solution in CH3CN and aq. NH3-solution yielded 36.6 mg (55.2 μmol, 100%) of the bisammonia-salt of 3-(4-(Carboxymethoxy)-2,2″-diisobutyl-3-naphthalen-1-ylmethyl-[1,1′:4′,1″]-terphenyl-4″-yl)propionic acid (80) as a white solid. Rf (hexanes/EtOAc (1+1), sample dissolved in HOAc)=0.49. 1H-NMR (500 MHz, d4-MeOH): δ=0.43 (d, 6H, J=6.62 Hz, 2*CH3), 0.65 (d, 6H, J=6.62 Hz, 2*CH3), 1.35 (m, 1H, CH), 1.58 (m, 1H, CH), 2.14 (d, 2H, J=7.41 Hz, CH2), 2.44 (d, 2H, J=7.25 Hz, CH2), 2.56 (t, 2H, J=7.41 Hz, CH2CH2CO2NH4), 2.90 (t, 2H, J=7.57 Hz, CH2CH2NH4), 4.58 (s, 2H, CH2Naphthyl), 4.59 (s, 2H, OCH2CO2NH4), 6.62 (d, 1H, J=2.05 Hz), 6.89-7.08 (m, 8H), 7.38-7.45 (m, 4H), 7.73 (m, 1H), 7.83 (m, 1H), 8.08 (m, 1H). 13C-NMR (125 MHz, d4-MeOH): δ=22.97, 23.13, 30.75, 31.02, 32.69, 33.91, 38.49, 43.45, 43.73, 68.54, 112.71, 126.33, 126.85, 126.92, 126.99, 127.26, 128.00, 128.35, 129.01, 129.22, 129.90, 130.84, 131.09, 131.41, 131.49, 132.31, 132.42, 134.19, 135.91, 135.95, 138.60, 140.16, 140.53, 141.56, 141.86, 142.22, 142.28, 157.00, 177.34, 178.03. MS (FAB−): m/z=629 (18), 628 (29), 627 (54), 570 (42), 569 (100), 568 (16), 567 (24), 527 (24), 526 (30), 525 (70), 524 (30), 523 (58), 481 (30), 347 (14), 153 (96). HR-MS (FAB−): not possible.

Sources & evidence

ORD record
ord-2ef9bba2357243bcbd2780dc1a88b8b0
Source dataset
uspto-grants-2005_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06858600B2

Reaction notes

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