Anisole → HCID 178518755, compound

HRID 1727324Notes

Reaction equation

HRID 1727324 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].C1(OC)C=CC=CC=1.N(CC1C=CC(OC)=CC=1)=[N+]=[N-].[F:25][C:26]1[C:27](=[O:47])[NH:28][C:29](=[O:46])[N:30]([C@H:32]2[CH2:35][C@@H:34]([CH2:36][CH2:37][O:38]CC3C=CC=CC=3)[CH2:33]2)[CH:31]=1>CO>[F:25][C:26]1[C:27](=[O:47])[NH:28][C:29](=[O:46])[N:30]([C@H:32]2[CH2:35][C@@H:34]([CH2:36][CH2:37][OH:38])[CH2:33]2)[CH:31]=1

Participants

5

Reactant 3

HCID 7519Anisole2×HCID 6451240Aluminum(III) Chloride2×HCID 178491256HCID 178491256, compound

Product 1

HCID 178518755HCID 178518755, compoundYield 53.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

In a 10 mL flask with AlCl3 (0.81 g, 6.2 mmol) inside, dry anisole 3 mL was added under argon to give a light yellow solution. In another flask with N3-PMB -5-fluoro-1-[cis-3-(benzyloxyethyl)cyclobutyl]uracil (0.27 g, 0.62 mmol) inside, dry anisole 2 mL was added, after which time AlCl3 solution was added to it slowly at room temperature by syringe pump. After addition finishes, the mixture was cooled to 0° C. and dry MeOH was added slowly to give a colorless solution at the end. Then the solvents were removed and the product was purified by silica gel flash chromatography (CH2Cl2:MeOH=20:1) to give a white solid (73.7 mg, 53.4%) combined with some three-membered ring by-products. 1H NMR (CD3OD, 300 MHz): δ 1.68-1.74 (m, 2H), 1.86-1.95 (m, 2H), 2.11-2.20 (m, 1H), 2.48-2.55 (m, 2H), 3.52-3.59 (m, 2H), 4.57-4.69 (m, 1H), 7.90-7.93 (d, J=6.9, 1H). 13C NMR (CDCl3, 100 MHz): δ 10.02, 10.93, 15.94, 18.55, 26.78, 36.15, 37.49, 40.11, 47.47, 53.57, 61.10, 62.87, 127.81, 128.14, 131.01, 131.35, 140.70, 143.01, 151.84, 152.19, 160.41. MS (FAB): expected for C10H13FN2O3 (M+H)+ 229.22. Found 229.09835. IR (neat) νmax 3411, 3187, 3063, 2934, 1697, 1473, 1357, 1272, 1243, 1043, 899, 807, 751, 704.

Workup

  1. customto give a light yellow solution
  2. additionAfter addition finishes
  3. customto give a colorless solution at the end
  4. customThen the solvents were removed
  5. customthe product was purified by silica gel flash chromatography (CH2Cl2:MeOH=20:1)

Sources & evidence

ORD record
ord-0570e02260cb4b8ebf28077d3bf6482a
Source dataset
uspto-grants-2009_02
Patent number
US07495006B2

Reaction notes

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