Ethyl Acetate → HCID 86683828, compound

HRID 1261433Notes

Reaction equation

HRID 1261433 reaction equation
[CH3:1][O:2][C:3](=[O:22])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16](=[CH2:20])[CH2:17][CH2:18][NH2:19])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:21])[CH:11]=2)[CH:6]=1.[Cl:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[S:30](Cl)(=[O:32])=[O:31].C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>C1COCC1>[CH3:1][O:2][C:3](=[O:22])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16](=[CH2:20])[CH2:17][CH2:18][NH:19][S:30]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[Cl:23])(=[O:32])=[O:31])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:21])[CH:11]=2)[CH:6]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 761872-Chlorobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86683826HCID 86683826, compound

Product 1

HCID 86683828HCID 86683828, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of [4-(3-amino-1-methylene-propyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (120 mg, 0.398 mmol) in THF (4 mL) was cooled to 0° C. and the solid 2-chlorobenzene-1-sulfonyl chloride (168 mg, 0.796 mmol) was added followed by N,N-diisopropylethylamine (154 mg, 209 μL, 1.19 mmol). After stirring for 2 hours at 0° C., the cooling bath was removed and the reaction mixture was warmed to room temperature. The reaction mixture was stirred at room temperature for 15 hours, then diluted with water and brine. The resulting mixture was extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated to afford a viscous oil. Flash chromatography (40 g ISCO column, 100% hexanes ramped to 50% ethyl acetate in hexanes) provided {4-[3-(2-chloro-benzenesulfonylamino)-1-methylene-propyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester as a viscous oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.04-8.07 (m, 1H), 7.74 (dd, J=9.00, 5.80 Hz, 1H), 7.62 (s, 1H), 7.49-7.54 (m, 2H), 7.40 (dd, J=7.65, 2.89 Hz, 1H), 7.32 (dd, J=11.20, 2.60 Hz, 1H), 7.19 (td, J=8.60, 2.40 Hz, 1H), 5.52 (q, J=1.40 Hz, 1H), 5.08-5.10 (m, 1H), 5.03 (t, J=6.40 Hz, 1H), 3.80 (s, 2H), 3.73 (s, 3H), 3.09-3.16 (m, 2H), 2.51 (t, J=7.00 Hz, 2H), 2.31 (s, 3H). MS cald. for C24H24ClFNO4S [(M+H)+] 476.1, obsd. 476.1.

Workup

  1. customthe cooling bath was removed
  2. temperaturethe reaction mixture was warmed to room temperature
  3. stirringThe reaction mixture was stirred at room temperature for 15 hours
  4. additiondiluted with water and brine
  5. extractionThe resulting mixture was extracted with ethyl acetate (2×50 mL)
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford a viscous oil

Sources & evidence

ORD record
ord-4c44755f51b646999d8f6e224d14bdeb
Source dataset
uspto-grants-2013_06
Patent number
US08470884B2

Reaction notes

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