Triethylamine → (R)-3,5-difluoro-N-(4-(1-(1-methylethylsulfonamido)propan-2-yl)phenyl)benzamide

HRID 2085447Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2085447
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]([CH3:19])[CH2:11][NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])=[CH:6][CH:5]=1)([O-])=O.C(N(CC)CC)C.[F:27][C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([F:37])[CH:36]=1)[C:31](Cl)=[O:32]>C(Cl)Cl>[CH3:19][C@H:10]([C:7]1[CH:8]=[CH:9][C:4]([NH:1][C:31]([C:30]2[CH:29]=[C:28]([F:27])[CH:36]=[C:35]([F:37])[CH:34]=2)=[O:32])=[CH:5][CH:6]=1)[CH2:11][NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 1456003,5-Difluorobenzoyl chlorideHCID 9965675(R)-N-(2-(4-nitrophenyl)propyl)propane-2-sulfonamide

Produkt 1

HCID 9843690(R)-3,5-difluoro-N-(4-(1-(1-methylethylsulfonamido)propan-2-yl)phenyl)benzamideAusbeute 80,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A 500 mL three necked round bottom flask equipped with a magnetic stirrer, thermometer, addition funnel and a positive nitrogen was charged with [(2R)-2-(4-nitrophenyl)propyl][(methylethyl)sulfonyl]amine (12.02 g, 46.85 mmol) and methylene chloride (200.0 mL). To this solution was added triethylamine (6.53 mL, 46.85 mmol) all at once. The solution was stirred for 10 minutes then added dropwise, neat 3,5difluorobenzoyl chloride (5.9 mL, 46.85 mmol) over a period of 20 minutes. The reaction exothermed to reflux by the end of addition. Stirred to room temperature over the weekend for convenience. Quenched reaction with 1 N HCl (100.0 mL) and separated lower organic layer. Washed the organic layer with 25% brine (70.0 mL) and dried with anhydrous magnesium sulfate. Filtered precipitates and concentrated filtrate to a tan oil (20.0 g). To this oil was added 1:1 ethyl acetate/hexane (125.0 mL) with stirring. A massive off white precipitate formed. The precipitate was then filtered and the cake washed with 1:1 ethyl acetate/hexane (50.0 mL). Precipitate was then dried in a house vacuum oven at 40° C. to provide N-[4-((1R)-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl](3,5-difluorophenyl)carboxamide (15.02 g, 80.9%); 1H NMR (CDCl3, 300 MHz) δ 1.26-1.27 (d, 6H), 1.29-1.30 (d, 2H), 2.92 (m, 1H), 3.10 (m, 1H), 3.20 (1H), 3.3-3.4 (m, 1H), 7.0 (triplet, 1H), 7.20 (d, 2H), 7.40 (d, 2H), 7.60 (m, 2H), 8.19 (s, 1H); 13C NMR (CDCl3, 300 MHz) δ 17.19, 17.30, 19.75, 41.03, 50.99, 54.15, 107.68, 107.86, 108.08, 111.12, 111.33, 121.81, 128.59, 136.97, 138.77, 140.51, 162.62, 162.71, 164.12, 164.61, 164.71.

Aufarbeitung

  1. additionthermometer, addition funnel
  2. additionthen added dropwise
  3. temperatureto reflux by the end of addition
  4. stirringStirred to room temperature over the weekend for convenience
  5. customQuenched
  6. customreaction with 1 N HCl (100.0 mL)
  7. customseparated lower organic layer
  8. washWashed the organic layer with 25% brine (70.0 mL)
  9. dry with materialdried with anhydrous magnesium sulfate
  10. filtrationFiltered
  11. customprecipitates
  12. additionTo this oil was added 1:1 ethyl acetate/hexane (125.0 mL)
  13. stirringwith stirring
  14. customA massive off white precipitate formed
  15. filtrationThe precipitate was then filtered
  16. washthe cake washed with 1:1 ethyl acetate/hexane (50.0 mL)
  17. customPrecipitate was then dried in a house vacuum oven at 40° C.

Quellen und Nachweise

ORD-Eintrag
ord-97d7e6cdebf740fb98cfae6b79fab93f
Quelldatensatz
uspto-grants-2004_04
Patentnummer
US06720357B2

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