Methanol → HCID 86686919, compound

HRID 2363878Notes

Reaction equation

HRID 2363878 reaction equation
[CH3:1][O:2][C:3](=[O:36])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:21][CH2:20][N:19]([S:22]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[N+:32]([O-])=O)(=[O:24])=[O:23])[CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:35])[CH:11]=2)[CH:6]=1.[Cl-].[NH4+].CO.O>[Zn].CCCCCC.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:36])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:17][CH2:18][N:19]([S:22]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[NH2:32])(=[O:24])=[O:23])[CH2:20][CH2:21]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:35])[CH:11]=2)[CH:6]=1

Participants

7

Reactant 4

HCID 887Methanol2×HCID 962WaterHCID 25517Ammonium Chloride2×HCID 86686918HCID 86686918, compound

Product 1

HCID 86686919HCID 86686919, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst3×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of {6-fluoro-3-methyl-4-[1-(2-nitro-phenylmethanesulfonyl)-piperidin-4-yl]-naphthalen-2-yl}-acetic acid methyl ester (505 mg, 0.981 mmol), zinc dust (325 mesh) (642 mg, 9.82 mmol), and ammonium chloride (787 mg, 14.7 mmol, was combined with methanol (10 mL) and water (5 mL) under nitrogen to create a suspension. Moderate heating using a heat gun was used to bring more of the starting material into solution, and more methanol (5 mL) was added. The suspension was stirred for two hours at which time LCMS and TLC analysis (1:1 hexane-ethyl acetate) analysis indicated the presence of unreacted starting material and a more polar product. Another 20 equivalents of zinc dust (1.02 g) was added and the reaction mixture was stirred for two hours with some heating with a heat gun during this time period. TLC analysis indicated that the reaction was not complete. Another 30 equivalents of ammonium chloride (1.4 g) was added and the resulting suspension was heated to 40-50° C. with a heating mantle. The reaction mixture was cooled to room temperature and the zinc was filtered-off and washed with methanol. The filtrate was concentrated and the residue was diluted with water. The suspension was extracted with ethyl acetate (2×75 mL) and the combined extracts were washed with brine, dried over MgSO4, filtered, and concentrated. Flash chromatography (80 g ISCO column, eluting with 0-70% ethyl acetate/hexanes) provided {4-[1-(2-amino-phenylmethanesulfonyl)-piperidin-4-yl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (385 mg, 81%) as a white solid. MS cald. for C26H30FN2O4S [(M+H)+] 484, obsd. 485.2.

Workup

  1. temperatureModerate heating
  2. additionwas added
  3. temperatureThe reaction mixture was cooled to room temperature
  4. washwashed with methanol
  5. concentrationThe filtrate was concentrated
  6. additionthe residue was diluted with water
  7. extractionThe suspension was extracted with ethyl acetate (2×75 mL)
  8. washthe combined extracts were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. washFlash chromatography (80 g ISCO column, eluting with 0-70% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4103b8d5eba1468e89aff16851630673
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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