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
Reaction equation
[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]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
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)
Workup
- extractionThe aqueous layer was extracted with CH2Cl2 (400 mL)
- washthe combined organic layers were washed with 0.4M NaOH
- dry with materialdried (Na2SO4)
- customevaporated under reduced pressure
Sources & evidence
- ORD record
- ord-7e0b51ef564d49b68d2bc8c0c2290af1
- Source dataset
- uspto-grants-2011_08
- Patent number
- US07989442B2
Reaction notes
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