Sodium Carbonate → HCID 57559119, compound

HRID 736065Notes

Reaction equation

HRID 736065 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[CH:16][C:17](Br)=[CH:18][C:19]=3[C:11]=2[CH2:10][CH2:9][NH:8][CH:7]=1)=[O:5])[CH3:2].[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCO.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:3][C:4]([C:6]1[C:12]2[NH:13][C:14]3[CH:15]=[CH:16][C:17]([C:26]4[CH:27]=[CH:28][C:23]([O:22][CH3:21])=[CH:24][CH:25]=4)=[CH:18][C:19]=3[C:11]=2[CH2:10][CH2:9][NH:8][CH:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 66640350HCID 66640350, compound

Product 1

HCID 57559119HCID 57559119, compoundYield 62.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 20074477Dimethoxyethane ethanolSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 9-bromo-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester (0.20 g, 0.60 mmol), (o-tolyl)3P (0.19 g, 0.6 mmol) and 4-methoxyphenylboronic acid (0.23 g, 1.5 mmol) in DME/EtOH (1:1, 12 mL) was added 2.1 mL of 1M Na2CO3 solution and Pd(OAc)2 (27 mg) at ambient temperature. The reaction mixture was heated at 80° C. under N2 for 1 hour and monitored by LC-MS. The solution was diluted with DCM (20 mL), and washed with brine. The aqueous phase was extracted with DCM (20 mL) twice. The combined organic phase was dried over Na2SO4 and concentrated. The crude product was purified by flash chromatograph on silica gel, eluting with EtOAc-hexane (0-30%) to yield the title compound (0.136 g) as a light yellow solid; 1H-NMR (CDCl3): δ 10.41 (1H, s), 7.73 (1H, d), 7.50 (3H, m), 7.29 (1H, d), 7.21 (1H, d), 6.90 (2H, m), 5.23(1H, s), 4.20 (2H, dd), 3.76 (3H, s), 3.55 (2H, m), 3.12 (2H, m), 1.26 (3H, t); MS (ESI): 363 (MH+).

Workup

  1. washwashed with brine
  2. extractionThe aqueous phase was extracted with DCM (20 mL) twice
  3. dry with materialThe combined organic phase was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatograph on silica gel
  6. washeluting with EtOAc-hexane (0-30%)

Sources & evidence

ORD record
ord-051e67ea8e114c90948fcc986d9fb9e8
Source dataset
uspto-grants-2009_09
Patent number
US07595311B2

Reaction notes

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