Potassium Bromide → HCID 66580034, compound

HRID 2368811Notes

Reaction equation

HRID 2368811 reaction equation
[OH:1][CH:2]1[CH2:25][CH2:24][C:5]2([C:9](=[O:10])[N:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C@H:18]([CH3:23])[C:19]([F:22])([F:21])[F:20])=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[CH2:4][CH2:3]1.CC1(C)N([O])C(C)(C)CCC1.[Br-].[K+].Cl[O-].[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.O.CC1(C)N([O])C(C)(C)CCC1>[F:22][C:19]([F:20])([F:21])[C@@H:18]([CH3:23])[O:17][C:14]1[CH:15]=[CH:16][C:11]([N:8]2[CH2:7][CH2:6][C:5]3([CH2:4][CH2:3][C:2](=[O:1])[CH2:25][CH2:24]3)[C:9]2=[O:10])=[CH:12][CH:13]=1

Participants

9

Reactant 5

HCID 253877Potassium BromideHCID 516892Sodium BicarbonateHCID 2724126TempoHCID 23665760Sodium Hypochlorite2×HCID 66580196HCID 66580196, compound

Product 1

HCID 66580034HCID 66580034, compoundYield 95%

Reagents, catalysts & solvents 3

HCID 2724126TempoCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 8-hydroxy-2-[4-((R)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-2-aza-spiro[4.5]decan-1-one (5.79 g) and 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) (506 mg) in CH2Cl2 (85 ml) was added a solution of potassium bromide (482 mg) in water (16 mL). Then, sodiumhypochlorite (13%, 42.5 mL) was added dropwise over a period of 10 minutes followed by sodium bicarbonate (NaHCO3) (4.08 g). The mixture was stirred for 1.5 h at RT. TLC showed a remainder of starting material. More TEMPO (125 mg) and sodiumhypochlorite solution (10 mL) were added to the reaction mixture and the mixture was stirred for additional 2 h at RT. The reaction mixture was poured into ice/water and was extracted three times with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The crude material was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to provide the title compound as a light brown solid (5.47 g). MS (m/e): 356.1 (MH+).

Workup

  1. stirringthe mixture was stirred for additional 2 h at RT
  2. extractionwas extracted three times with CH2Cl2
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent was evaporated
  7. customThe crude material was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-fe7c3af33c7e47a2abf2161f01bdc1eb
Source dataset
uspto-grants-2014_04
Patent number
US08703807B2

Reaction notes

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