Imidazole → Benzoic acid, 4-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-

HRID 2306846Notes

Reaction equation

HRID 2306846 reaction equation
[OH:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1.[Si:12](Cl)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].N1C=CN=C1>C(O)(=O)C.N1C=CC=CC=1.CN(C=O)C.[H][H].[Pd]>[O:1]([CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([OH:9])=[O:8])=[CH:10][CH:11]=1)[Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Participants

8

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 763604-(Hydroxymethyl)benzoic acid

Product 1

HCID 11747545Benzoic acid, 4-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-Yield 65%

Reagents, catalysts & solvents 4

HCID 178506449HCID 178506449, compoundCatalystHCID 176Acetic AcidSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

The photolabile linker was prepared as described by Holmes et al. in J. Org. Chem., 60: 2318-2319 (1995). 2-methoxy-4-acetylphenol was treated with Br—(CH2)3—CO2CH3 and K2CO3 in DMF and the product was reacted with excess hydroxylamine hydrochloride/pyridine/H2O. The oxime formed was reduced with H2/Pd/C in acetic acid and the resulting amine trifluoroacetylated with the anhydride in pyridine. The product was crystallized from ethanol water (80% four steps). The product was nitrated with concentrated nitrous acid in acetic acid (86%). The protecting groups were removed by reflux in NaOH/MeOH/H2O and the crude product was reacted with Fmoc chloride (81%). 4-[(tert-butyldimethylsiloxy)methyl]benzoic acid (TBDMS-HMBA) was prepared as described by Kita et al. in J. Org. Chem., 51: 4150-4158 (1986). 4-(hydroxymethyl)-benzoic acid (0.76 g, 5 mmol) was reacted with tert-butyldimethylsilyl chloride (2.29 g, 15 mmol) and imidazole (2.04 g, 30 mmol) in dry DMF (12 mL). Aqueous workup gave (0.86 g) 65% yield of the 4-[(tert-butyldimethylsiloxy)methyl]benzoic acid with melting point 157-159° C., δppm 8.06 (d, J=8 Hz); 7.39(d, J=8 Hz); 4.78 (s); 0.94 (s); 0.11 (s).

Workup

  1. customThe product was crystallized from ethanol water (80% four steps)
  2. customThe protecting groups were removed
  3. temperatureby reflux in NaOH/MeOH/H2O
  4. customthe crude product was reacted with Fmoc chloride (81%)
  5. custom4-[(tert-butyldimethylsiloxy)methyl]benzoic acid (TBDMS-HMBA) was prepared

Sources & evidence

ORD record
ord-de3a59b0f7974e9585e21470bf3469c9
Source dataset
uspto-grants-2004_12
Patent number
US06828392B2

Reaction notes

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