Methane → tert-butyl 5-(2,4-dichlorophenyl)-1,2,6b,7,8,10,11,11a-octahydro-9H-azepino[4,5-b][1,4]oxazino[2,3,4-hi]indole-9-carboxylate

HRID 51057Notes

Reaction equation

HRID 51057 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([O:11][CH2:12][CH2:13][N:7]3[CH:6]3[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18][CH:5]23)[CH:10]=1.[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1B(O)O.C>>[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([O:11][CH2:12][CH2:13][N:7]3[CH:6]3[CH2:14][CH2:15][NH:16][CH2:17][CH2:18][CH:5]23)[CH:10]=1.[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([O:11][CH2:12][CH2:13][N:7]3[CH:6]3[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:17][CH2:18][CH:5]23)[CH:10]=1

Participants

5

Reactant 3

HCID 297MethaneHCID 2734659(2,4-Dichlorophenyl)boronic acidHCID 22735371tert-butyl 5-bromo-1,2,6b,7,8,10,11,11a-octahydro-9H-azepino[4,5-b][1,4]oxazino[2,3,4-hi]indole-9-carboxylate

Product 2

HCID 227355075-(2,4-dichlorophenyl)-1,2,7,8,9,10,11,11a-octahydro-6bH-azepino[4,5-b][1,4]oxazino[2,3,4-hi]indoleHCID 22735562tert-butyl 5-(2,4-dichlorophenyl)-1,2,6b,7,8,10,11,11a-octahydro-9H-azepino[4,5-b][1,4]oxazino[2,3,4-hi]indole-9-carboxylateYield 129.5%

Procedure

Tert-butyl 5-(2,4-dichlorophenyl)-1,2,6b,7,8,10,11,11a-octahydro-9H-azepino[4,5-b][1,4]oxazino[2,3,4-hi]indole-9-carboxylate (510 mg, 65%) was prepared via coupling of tert-butyl 5-bromo-1,2,6b,7,8,10,11,11a-octahydro-9H-azepino[4,5-b][1,4]oxazino[2,3,4-hi]indole-9-carboxylate (671 mg, 1.64 mmol) with 2,4-dichlorophenyl boronic acid (470 mg, 2.46 mmol) as illustrated by the general procedure described in Example 534 Step C. 1H NMR (CDCl3, 300 MHz) δ1.48 (s, 9H), 1.81-2.22 (m, 4H), 2.80-3.00 (m, 1H), 3.25 (d, 1H, J=11.5 Hz), 3.31-3.75 (m, 6H), 4.49-4.50 (m, 2H), 6.66 (s, 1H), 6.72 (s, 1H), 7.23 (s, 2H), 7.43 (s, 1H) ppm. CIMS (Methane) m/z=476 [MH]+. The corresponding hydrochloride salt of the title compound was formed from tert-butyl 5-(2,4-dichlorophenyl)-1,2,6b,7,8,10,11,11a-octahydro-9H-azepino[4,5-b][1,4]oxazino[2,3,4-hi]indole-9-carboxylate (505 mg) using the procedure described in Example 534 Step D. Then, this salt was free-based using 6 N NaOH, to give the title compound (398 mg, 99%). 1H NMR (CDCl3, 300 MHz) δ1.60-2.30 (m, 5H), 2.70-3.30 (m, 6H), 3.40-3.60 (m, 1H), 3.70-3.80 (m, 1H), 4.30-4.60 (m, 2H), 6.70 (s, 1H), 6.73 (s, 1H), 7.28 (s, 1H), 7.29 (s, 1H), 7.43 (s, 1H) ppm. CIMS (Methane) m/z=376 [MH]+.

Sources & evidence

ORD record
ord-ceadbab44d164f8f9b95a00ef4bb91f6
Source dataset
uspto-grants-2004_03
Patent number
US06713471B1

Reaction notes

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