Diisopropylethylamine → HCID 86686918, compound

HRID 2363876Notes

Reaction equation

HRID 2363876 reaction equation
[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:22])[CH:11]=2)[CH:6]=1.[N+:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH2:33][S:34](Cl)(=[O:36])=[O:35])([O-:26])=[O:25].C(N(CC)C(C)C)(C)C>C1COCC1.O.[Cl-].[Na+].O>[CH3:1][O:2][C:3](=[O:23])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH:16]2[CH2:17][CH2:18][N:19]([S:34]([CH2:33][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N+:24]([O-:26])=[O:25])(=[O:35])=[O:36])[CH2:20][CH2:21]2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:22])[CH:11]=2)[CH:6]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 4305447(2-nitrophenyl)methanesulfonyl ChlorideHCID 86686890HCID 86686890, compound

Product 1

HCID 86686918HCID 86686918, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A light brown solution of (6-fluoro-3-methyl-4-piperidin-4-yl-naphthalen-2-yl)-acetic acid methyl ester (which may be prepared as described above; 560 mg, 1.78 mmol) and (2-nitrophenyl)methanesulfonyl chloride (837 mg, 3.55 mmol) in THF (30 mL) was cooled to 0° C. under nitrogen and then N,N-diisopropylethylamine (930 μL, 5.34 mmol) was added. The resulting light brown solution was stirred for 2 hours at 0° C. temperature and then allowed to warm to room temperature and stirred for 36 hours. The reaction mixture was diluted with water and brine and the organic compound was extracted into ethyl acetate (2×100 mL). The combined organic layers were washed with brine and dried over MgSO4, filtered, and concentrated. The crude product was purified using flash chromatography (120 g ISCO column eluting with 0-60% ethyl acetate/hexanes) to give {6-fluoro-3-methyl-4-[1-(2-nitro-phenylmethanesulfonyl)-piperidin-4-yl]-naphthalen-2-yl}-acetic acid methyl ester (645 mg, 71%) as a light yellow solid. 1H NMR (400 MHz, Chloroform-d) δ 8.07-8.1 (m, 1H), 7.85 (br. s, 1H), 7.55 (dd, J=8.8, 6.3 Hz, 1H), 7.67-7.72 (m, 2H), 7.56-7.64 (m, 2H), 7.16-7.24 (m, 1H), 4.83 (s, 2H), 3.89 (d, J=10.0 Hz, 2H), 3.82 (br. s, 2H), 3.72 (s, 3H), 3.43-3.63 (m, 1H), 2.90 (t, J=11.5 Hz, 2H), 2.32-2.71 (m, 5H), 1.77 (d, J=13.8 Hz, 2H). MS cald. for C26H27FN2O6S [(M+H)+] 514, obsd. 515.2.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 36 hours
  3. extractionthe organic compound was extracted into ethyl acetate (2×100 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified
  9. washflash chromatography (120 g ISCO column eluting with 0-60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-20fbd446f4854a3e922f7332abe27b5a
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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