Imidazole → Methyl 4-((3-(((tert-butyldimethylsilyl)oxy)methyl)adamantan-1-yl)methoxy)-5-chloro-2-fluorobenzoate

HRID 1849706Notes

Reaction equation

HRID 1849706 reaction equation
[Cl:1][C:2]1[C:3]([O:13][CH2:14][C:15]23[CH2:24][CH:19]4[CH2:20][CH:21]([CH2:23][C:17]([CH2:25][OH:26])([CH2:18]4)[CH2:16]2)[CH2:22]3)=[CH:4][C:5]([F:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[C:27]([Si:31](Cl)([CH3:33])[CH3:32])([CH3:30])([CH3:29])[CH3:28].N1C=CN=C1>CN(C)C=O.C(OCC)(=O)C>[Si:31]([O:26][CH2:25][C:17]12[CH2:23][CH:21]3[CH2:20][CH:19]([CH2:24][C:15]([CH2:14][O:13][C:3]4[C:2]([Cl:1])=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([F:12])[CH:4]=4)([CH2:22]3)[CH2:16]1)[CH2:18]2)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86703577Methyl 5-chloro-2-fluoro-4-((3-(hydroxymethyl)-adamantan-1-yl)methoxy)benzoate

Product 1

HCID 86703579Methyl 4-((3-(((tert-butyldimethylsilyl)oxy)methyl)adamantan-1-yl)methoxy)-5-chloro-2-fluorobenzoateYield 102%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 5-chloro-2-fluoro-4-((3-(hydroxymethyl)-adamantan-1-yl)methoxy)benzoate (0.83 g, 2.17 mmol), tert-butylchlorodimethylsilane (0.36 g, 2.39 mmol), and imidazole (0.74 g, 10.90 mmol) in anhydrous dimethylformamide (12 mL) was stirred at ambient temperature under nitrogen for 16 hours. The reaction mixture was diluted with ethyl acetate (100 mL), washed with water (50 mL), saturated ammonium chloride (2×50 mL) and brine (2×50 mL); dried with anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (8:1 hexanes:ethyl acetate) to provide the title compound (1.10 g, quant): 1H NMR (300 MHz, CDCl3) δ 7.93 (d, J=7.6 Hz, 1H), 6.62 (d, J=12.1 Hz, 1H), 3.87 (s, 3H), 3.58 (s, 2H), 3.17 (s, 2H), 2.13-2.05 (m, 2H), 1.69-1.58 (m, 6H), 1.49-1.36 (m, 6H), 0.87 (s, 9H), −0.01 (s, 6H); MS (ES+) m/z 497.1, 499.1 (M+1).

Workup

  1. washwashed with water (50 mL), saturated ammonium chloride (2×50 mL) and brine (2×50 mL)
  2. dry with materialdried with anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (8:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-ed7922b9cbef4b76b708f83131e577c3
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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