Methyl morpholine oxide → Methyl (5r,6s)-rel-13-cyclohexyl-6,7-dihydro-5,6-dihydroxy-5h-indolo[2,1-a][2]benzazepine-10-carboxylate

HRID 860739Notes

Reaction equation

HRID 860739 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:25]([O:27][CH3:28])=[O:26])=[CH:12][C:13]=3[N:14]3CC=C[C:17]4[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[N+]1([O-])CC[O:33]CC1.[CH3:37][C:38]([CH3:40])=[O:39].O>S([O-])([O-])(=O)=S.[Na+].[Na+].O=[Os](=O)(=O)=O>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:25]([O:27][CH3:28])=[O:26])=[CH:12][C:13]=3[N:14]3[CH2:40][C@H:38]([OH:39])[C@H:37]([OH:33])[C:17]4[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 82029Methyl morpholine oxideHCID 11667856methyl 13-cyclohexyl-7H-indolo[2,1-a][2]benzazepine-10-carboxylateHCID 18366337Propan-2-one--water (1/1)

Product 1

HCID 69207219Methyl (5r,6s)-rel-13-cyclohexyl-6,7-dihydro-5,6-dihydroxy-5h-indolo[2,1-a][2]benzazepine-10-carboxylateYield 91%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 24477Sodium ThiosulfateSolvent

Procedure

OsO4 (23 mg, 0.09 mmol) was added to a stirred solution of methyl 13-cyclohexyl-7H-indolo{2,1-a][2]benzazepine-10-carboxylate (341 mg, 0.92 mmol) and 4-methyl-morpholine N-oxide(430 mg, 3.68 mmol) in acetone-water (50 mL-6 mL) at rt. The reaction mixture was stirred at rt for 18 hr and then diluted with aqueous sodium thiosulfate. The mixture was extracted with ethyl acetate. The organic layer was washed with brine (3×) and dried over sodium sulfate, filtered and evaporated under reduced pressure. The crude product was purified utilizing a Biotage apparatus with a prepacked silica column and using gradients of hexanes:ethyl acetate of from (98:2) to (80:20) to afford the product as a light yellow solid (340 mg, 91%). ESI-MS m/z 406 (MH+); 1H NMR (500 MHz, MeOD) δ 1.25 (m, 1 H) 1.43 (m, 2 H) 1.58 (d, J=13.12 Hz, 1 H) 1.77 (d, J=8.85 Hz, 2 H) 2.02 (m, 4 H) 2.93 (m, 1 H) 3.31 (m, 1 H) 3.93 (s, 3 H) 4.40. (d, J=4.58 Hz, 1 H) 4.52 (m, 1 H) 4.68 (dd, J=14.19, 7.17 Hz, 1 H) 7.40 (t, J=7.32 Hz, 1 H) 7.44 (t, J=7.32 Hz, 1 H) 7.51 (t, J=7.48 Hz, 1 H) 7.70 (d, J=8.55 Hz, 1 H) 7.78 (d, J=7.63 Hz, 1 H) 7.86 (d, J=8.55 Hz, 1 H) 8.15 (s, 1 H).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with brine (3×)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-39ac5afe6e384f05ae655de3decc42b6
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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