Acetic Acid → (2S,4S)-4-(3-(2-Chloro-4-fluoro-benzoylamino)-phenylamino)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 1591894Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1591894
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:18])[C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:6][CH:7]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][C@@H:27]1[CH3:33])=[O:25])([CH3:22])([CH3:21])[CH3:20].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1.CO>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C@H:29]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][C:9](=[O:18])[C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=3[Cl:17])[CH:3]=2)[CH2:28][C@@H:27]1[CH3:33])=[O:25])([CH3:22])([CH3:20])[CH3:21]

Komponenten

7

Edukt 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 11401606tert-butyl (2S)-2-methyl-4-oxopiperidine-1-carboxylateHCID 16775600N-(3-Aminophenyl)-2-chloro-4-fluorobenzamide

Produkt 1

HCID 58997317(2S,4S)-4-(3-(2-Chloro-4-fluoro-benzoylamino)-phenylamino)-2-methyl-piperidine-1-carboxylic acid tert-butyl esterAusbeute 46,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Dissolve N-(3-amino-phenyl)-2-chloro-4-fluoro-benzamide (Preparation 1, 200 mg, 0.756 mmol) and (2S)-2-methyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester (161 mg, 0.756 mmol) in tetrahydrofuran (5 mL). Add acetic acid (52 μL, 0.907 mmol) and sodium triacetoxyborohydride (192 mg, 0.907 mmol) and stir at room temperature for 18 hr. Heat the reaction to 45° C. for 4 hr. Cool the reaction to room temperature and load onto an SCX column with methanol. Wash the column with methanol, flush with 2M ammonia in methanol, and concentrate in vacuo. Purify by column chromatography (20%–75% ethyl acetate/hexane) to yield 161 mg (46%) of the title compound. Mass spectrum (ion spray): m/z 462.4 (M+1); 1H NMR: δ (CDCl3, ppm) 7.76 (m, 2H), 7.20 (m, 1H), 7.15 (m, 1H), 7.10 (m, 1H), 6.70 (d, J=7.6 Hz, 1H), 6.40 (d, J=8.4 Hz, 1H), 4.20 (m, 1H), 3.82 (m, 2H), 3.67 (bs, 1H), 3.20 (m, 1H), 2.00 (m, 2H), 1.65 (m, 2H), 1.47 (s, 9H), 1.27, (m, 4H).

Aufarbeitung

  1. temperatureHeat
  2. customthe reaction to 45° C. for 4 hr
  3. temperatureCool
  4. customthe reaction to room temperature
  5. washWash the column with methanol
  6. customflush with 2M ammonia in methanol
  7. concentrationconcentrate in vacuo
  8. customPurify by column chromatography (20%–75% ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-156613de07cc4314ae2fff6785406328
Quelldatensatz
uspto-grants-2007_11
Patentnummer
US07291632B2

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