Sodium Hydroxide → (-)-(cis)-7-bromo-8-fluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-amine

HRID 1668350Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1668350
[OH-].[Na+].OP1(=O)O[C@@H](C2C=CC=CC=2)C(C)(C)CO1.[Br:19][C:20]1[C:39]([F:40])=[CH:38][C:23]2[O:24][C:25]3[CH:37]=[CH:36][CH:35]=[CH:34][C:26]=3[C@H:27]3[C@H:32]([NH2:33])[CH2:31][CH2:30][CH2:29][N:28]3[C:22]=2[CH:21]=1>C(O)C.C(Cl)Cl>[Br:19][C:20]1[C:39]([F:40])=[CH:38][C:23]2[O:24][C:25]3[CH:37]=[CH:36][CH:35]=[CH:34][C:26]=3[C@H:27]3[C@H:32]([NH2:33])[CH2:31][CH2:30][CH2:29][N:28]3[C:22]=2[CH:21]=1

Komponenten

4

Edukt 2

HCID 14798Sodium HydroxideHCID 67359988(-)-(cis)-7-bromo-8-fluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-amine (4S)-2-hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinane 2-oxide

Produkt 1

HCID 67358773(-)-(cis)-7-bromo-8-fluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-amineAusbeute 100 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21584144Dichloromethane ethanolLösungsmittel

Versuchsvorschrift

1M NaOH (580 ml, 580 mmol) was added to a solution of (−)-(cis)-7-bromo-8-fluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-amine (4S)-2-hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinane 2-oxide (1:1) (45,42 g 75 mmol) in 1L of ethanol:CH2Cl2 (1:9), and the resulting biphasic mixture was vigorously stirred at ambient temperature for 0.5 h. The aqueous layer was extracted with CH2Cl2 (400 mL) and the combined organic layers were washed with 0.4M NaOH, dried (Na2SO4) and evaporated under reduced pressure to yield the title compound (27.2 g, 100%). 1H-NMR (400 MHz, CDCl3) 1.40-1.51 (m, 1H), 1.69-1.89 (m, 2H), 2.14-2.22 (m, 1H), 3,11-3.29 (m, 1H), 3.38-3.45 (m, 1H), 3.68-3.76 (m, 2H), 6.87-6.90 (d, J=8.0, 1H), 7.03-7.30 (m, 5H). 19F-NMR (400 MHz, CDCl3) −118.27. (m/z)=363+365 (M+H)+. (e.e. =99.9%) (chiralpak AD-H 25*0.46 cm, heptane:ethanol=8:2). (m/z)=363+365 (M+H)+. [α]D20.5=−202° (c=1.0, CHCl3)

Aufarbeitung

  1. extractionThe aqueous layer was extracted with CH2Cl2 (400 mL)
  2. washthe combined organic layers were washed with 0.4M NaOH
  3. dry with materialdried (Na2SO4)
  4. customevaporated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-7e0b51ef564d49b68d2bc8c0c2290af1
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07989442B2

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