Oxygen → HCID 86695134, compound

HRID 1503966Notes

Reaction equation

HRID 1503966 reaction equation
[CH3:1][N:2]([CH:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[N:18]=[CH:19][N:20]=[C:21]3[C:28]=2[C:27]2[C@@H:26]([CH2:29][CH:30]=[O:31])[CH2:25][CH2:24][C:23]=2[S:22]3)[CH2:12][CH2:11]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].B([CH2:37][CH3:38])(CC)CC.[C:39]([O:43]O)(C)(C)[CH3:40].O=O.[NH4+].[OH-]>C1COCC1>[OH:31][C@H:30]([C@@H:38]1[CH2:37][CH2:40][CH2:39][O:43]1)[CH2:29][C@H:26]1[CH2:25][CH2:24][C:23]2[S:22][C:21]3[C:28](=[C:17]([O:16][CH:13]4[CH2:14][CH2:15][CH:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:6])[CH3:7])[CH2:11][CH2:12]4)[N:18]=[CH:19][N:20]=3)[C:27]1=2

Participants

7

Reactant 5

HCID 977OxygenHCID 6410tert-Butyl hydroperoxide2×HCID 7357Triethylborane2×HCID 14923Ammonium HydroxideHCID 86695117HCID 86695117, compound

Product 1

HCID 86695134HCID 86695134, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

For the preparation of the starting material compound 43.1, please refer to Example 43. A 50-mL three necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was charged with a solution of tert-butyl N-methyl-N-(4-[[(3R)-3-(2-oxoethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]oxy]cyclohexyl)carbamate (500 mg, 1.12 mmol, 1.00 equiv) in 10 mL of distilled THF. Et3B (11.2 mL, 1N) was added slowly at 0° C. over 20 min. Then t-BuOOH (1.225 mL) was added dropwise to the mixture at the same temperature. After being stirred for 10 min, the mixture was allowed to warmed to room temperature and stirring was continued for an additional period during which the reaction proceeded to completion (Caution: Triethylborane, a liquid pyrophoric toward oxygen, should be handled so as to avoid exposure to air. The addition of tert-butyl hydroperoxide to trialkylboranes may lead to highly exothermic reactions and gas evolution. We encountered no violent reaction with the present procedures, but special care is advised.) The reaction mixture was treated with 28% NH4OH and extracted with CH2Cl2. (A 28% NH4OH solution allows the removal of unidentified polar materials possibly derived from Et3B. Removal of polar byproducts in the crude mixture, detectable on an iodine/silica gel TLC plate, may otherwise be difficult. The crude mixture must thus be washed with 28% NH4OH for adequate purification.) The extracts were washed with saturated aqueous NaHSO3 and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5) to provide tert-butyl N-(4-[[(3R)-3-[(2S)-2-hydroxy-2-[(2S)-oxolan-2-yl]ethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (230 mg, 40%) as a colorless oil. MS (ES): m/z 518 [M+H]+.

Workup

  1. customA 50-mL three necked round-bottom flask, purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringstirring
  4. waitwas continued for an additional period during which
  5. customno violent reaction with the present procedures, but special care
  6. extractionextracted with CH2Cl2
  7. customthe removal of unidentified polar materials
  8. customRemoval of polar byproducts in the crude mixture, detectable on an iodine/silica gel TLC plate
  9. washThe crude mixture must thus be washed with 28% NH4OH for adequate purification
  10. wash) The extracts were washed with saturated aqueous NaHSO3
  11. dry with materialdried over anhydrous sodium sulfate
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-ac34926f03c142b58e80d8791d359a81
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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