Hydrochloric Acid → 7-Bromo-5-(2-fluoro-phenyl)-3-methyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one

HRID 1435808Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1435808
C(OC(=O)[NH:7][CH:8]([C:10](=[O:28])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][C:13]=1[C:19](=O)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[F:26])[CH3:9])(C)(C)C.Cl>C(Cl)(Cl)Cl>[Br:18][C:15]1[CH:16]=[CH:17][C:12]2[NH:11][C:10](=[O:28])[CH:8]([CH3:9])[N:7]=[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[C:13]=2[CH:14]=1

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 68523676{1-[4-Bromo-2-(2-fluorobenzoyl)-phenylcarbamoyl]-ethyl)-carbamic acid tert-butyl ester

Produkt 1

HCID 685254147-Bromo-5-(2-fluoro-phenyl)-3-methyl-1,3-dihydro-benzo[e][1,4]diazepin-2-oneAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6212ChloroformLösungsmittel

Versuchsvorschrift

To a stirred solution of the benzophenone 116 (30 g, 64.4 mmol) in CHCl3 (300 mL) at rt, hydrogen chloride gas was added slowly. After 20 min, the addition was stopped and the solution was allowed to stir overnight at rt. The reaction mixture was washed with a saturated solution of sodium bicarbonate solution (2×70 mL) and water (2×70 mL). The organic layer was concentrated under reduced pressure. The residual oil was dissolved in methanol-water (1:1, 300 mL) and the pH was adjusted to 8.5 by the addition of aq sodium hydroxide (1 N). The reaction mixture was allowed to stir for 10 h at rt. The solution was then concentrated under reduced pressure and water (100 mL) was added. The solution was extracted with CH2Cl2 (3×50 mL), the organic layer was dried (Na2SO4) and concentrated under reduced pressure. The crude solid 11 was purified by recrystallization from methanol/water to provided 117 (17.8 g, 80%). mp 183-185° C.; IR (KBr, cm−1) 2928, 1694, 1611, 1479, 1450, 1377, 1315; 1H NMR (CDCl3) δ 9.50 (bs, 1H), 7.62-7.65 (m, 2H), 7.50 (q, J=6.5 Hz, 1H), 7.40 (d, J=2.0 Hz, 1H), 7.29 (t, J=7.5 Hz 1H) 7.15 (d, J=8.6 Hz, 1H), 7.11 (t, J=8.9 Hz, 1H), 3.84 (q, J=6.5 Hz, 1H), 1.82 (d, J=6.5 Hz, 3H); MS (EI) m/e (relative intensity) 348 (M++1, 23), 347 (M+, 38), 346 (24), 345 (36), 329 (19), 327 (20), 307 (40), 306 (41), 305(100), 304 (37), 303 (63); [α]26D=168.8 (c 0.73, EtOAc).

Aufarbeitung

  1. additionthe addition
  2. washThe reaction mixture was washed with a saturated solution of sodium bicarbonate solution (2×70 mL) and water (2×70 mL)
  3. concentrationThe organic layer was concentrated under reduced pressure
  4. dissolutionThe residual oil was dissolved in methanol-water (1:1, 300 mL)
  5. additionthe pH was adjusted to 8.5 by the addition of aq sodium hydroxide (1 N)
  6. stirringto stir for 10 h at rt
  7. concentrationThe solution was then concentrated under reduced pressure and water (100 mL)
  8. additionwas added
  9. extractionThe solution was extracted with CH2Cl2 (3×50 mL)
  10. dry with materialthe organic layer was dried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customThe crude solid 11 was purified by recrystallization from methanol/water

Quellen und Nachweise

ORD-Eintrag
ord-130a2588dd484dfeb7628911ff6b5701
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07618958B2

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