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 1668350노트

반응식

HRID 1668350 반응식
[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

참가 물질

4

반응물 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

생성물 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-amine수율 100%

시약·촉매·용매 1

HCID 21584144Dichloromethane ethanol용매

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-7e0b51ef564d49b68d2bc8c0c2290af1
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07989442B2

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