N-Fluorobenzenesulfonimide → methyl (+/-)-13-cyclohexyl-6,7-dihydro-6-carbomethoxy-6-fluoro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate

HRID 1394901Notes

Reaction equation

HRID 1394901 reaction equation
[Li+].CC([N-]C(C)C)C.[C:9]([CH:13]1[CH2:19][C:18]2[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=2[C:16]2=[C:24]([CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)[C:25]3[CH:26]=[CH:27][C:28]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][C:30]=3[N:15]2[CH2:14]1)([O:11][CH3:12])=[O:10].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:51])(=O)=O)=CC=1>C1COCC1>[CH:35]1([C:24]2[C:25]3[CH:26]=[CH:27][C:28]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][C:30]=3[N:15]3[CH2:14][C:13]([C:9]([O:11][CH3:12])=[O:10])([F:51])[CH2:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[C:16]=23)[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 588007N-FluorobenzenesulfonimideHCID 2724682Lithium diisopropylamideHCID 58765149dimethyl 13-cyclohexyl-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-6,10-dicarboxylate

Product 1

HCID 58677086methyl (+/-)-13-cyclohexyl-6,7-dihydro-6-carbomethoxy-6-fluoro-5H-indolo[2,1-a][2]benzazepine-10-carboxylateYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of LDA in THF (0.7 mL of 0.5 N, 0.35 mmol) was added to a solution of methyl (±)-6-carbomethoxy-13-cyclohexyl-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate (100 mg, 0.23 mmol) in THF (1 mL) at −78° C. Stirring was continued at −78° C. for 15 min and N-fluorobenzenesulfonimide (110 mg, 0.35 mmol) was added in one portion. The mixture was then slowly warmed to −0° C. and Stirring was continued for 1 hr at 0° C. The solution was quenched with MeOH. The solution was extracted with ethyl acetate and the extract washed with dilute HCl (2×), brine (3×), and then dried (Na2SO4). The extract was concentrated and the crude product purified on the Shimadzu preparative liquid chromatograph. The product containing fraction was concentrated on a Speed Vac® to leave the titled compound as a white solid (30 mg, 29%). ESI-MS m/z 449 (MH+).

Workup

  1. stirringStirring
  2. waitwas continued for 1 hr at 0° C
  3. customThe solution was quenched with MeOH
  4. extractionThe solution was extracted with ethyl acetate
  5. washthe extract washed with dilute HCl (2×), brine (3×)
  6. dry with materialdried (Na2SO4)
  7. concentrationThe extract was concentrated
  8. customthe crude product purified on the Shimadzu preparative liquid chromatograph
  9. additionThe product containing fraction
  10. concentrationwas concentrated on a Speed Vac®

Sources & evidence

ORD record
ord-29038c15bfff4ec9a4c8f1e0cd9f52bc
Source dataset
uspto-grants-2008_03
Patent number
US07348425B2

Reaction notes

Loading…