Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl ester → Benzyl 4-[3-acetyl-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-7-yl]piperidine-1-carboxylate

HRID 1785398Notes

Reaction equation

HRID 1785398 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[C:14]([CH:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)=[O:23])[CH2:18][CH2:17]4)[CH:13]=[CH:12][N:11]3[CH:32]=2)=[CH:4][CH:3]=1.[CH3:33][C:34](OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=[O:35]>S(=O)(=O)(O)O>[C:34]([C:32]1[N:11]2[CH:12]=[CH:13][C:14]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[CH2:18][CH2:17]3)=[CH:15][C:10]2=[N:9][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)(=[O:35])[CH3:33]

Participants

4

Reactant 2

HCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterHCID 58774430Benzyl 4-[2-(4-fluorophenyl)imidazo[1,2-a]pyridin-7-yl]piperidine-1-carboxylate

Product 1

HCID 58774431Benzyl 4-[3-acetyl-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-7-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidCatalyst

Conditions

Temperature
140 °C

Procedure

Imidazopyridine 34 (290 mg, 0.675 mmol) was dissolved in acetic (50 mL) in a 250 mL round bottom flask. Three drops of sulfuric acid were then added, and the reaction was heated to 140° C. for 24 hours. The reaction was then concentrated under reduced pressure, then diluted with both ethyl acetate and saturated sodium bicarbonate solution, and extracted repeatedly into ethyl acetate. Organic fractions were pooled, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was then dissolved in 5 mL methylene chloride, then loaded onto a 40 g Isco RediSep normal phase silica cartridge, and purified on an Isco OptiX10 CombiFlash instrument using a gradient that started at 100% heptane and ended at 100% ethyl acetate. Fractions containing desired product were pooled and concentrated under reduced pressure. Yield of 35: 180 mg (56%). 1H NMR (400 MHz, CDCl3) δ 1.67 (m, 2H), 1.92 (m, 2H), 2.17 (s, 3H), 2.81 (m, 1H), 2.93 (bs, 2H), 4.38 (bs, 2H), 5.16 (s, 2H), 6.48 (d, J=7.2 Hz, 1H), 6.96 (t, J=8.8 Hz, 2H), 7.24 (m, 5H), 7.57 (s, 1H), 7.76 (m, 2H), 7.86 (d, J=7.2 Hz, 1H). MS (ESI+) 472.2.

Workup

  1. concentrationThe reaction was then concentrated under reduced pressure
  2. additiondiluted with both ethyl acetate and saturated sodium bicarbonate solution
  3. extractionextracted repeatedly into ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe crude product was then dissolved in 5 mL methylene chloride
  8. custompurified on an Isco OptiX10 CombiFlash instrument
  9. additionFractions containing desired product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d22e45b0d2c44cec96c70cd36581360c
Source dataset
uspto-grants-2009_03
Patent number
US07504501B2

Reaction notes

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