tert-Butanol → HCID 67999573, compound

HRID 1048520Notes

Reaction equation

HRID 1048520 reaction equation
Cl([O-])=O.[Na+].[Cl:5][C:6]1[CH:7]=[C:8]([C@@H:12]2[C@@H:17]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[N:16]([C@@H:25]([CH:34]3[CH2:36][CH2:35]3)[CH2:26][NH:27][S:28]([CH:31]3[CH2:33][CH2:32]3)(=[O:30])=[O:29])[C:15](=[O:37])[C@@:14]([CH2:41][CH3:42])([CH2:38][CH:39]=[O:40])[CH2:13]2)[CH:9]=[CH:10][CH:11]=1.C([OH:47])(C)(C)C.C1COCC1>O.OP([O-])(O)=O.[K+]>[Cl:5][C:6]1[CH:7]=[C:8]([C@@H:12]2[C@@H:17]([C:18]3[CH:19]=[CH:20][C:21]([Cl:24])=[CH:22][CH:23]=3)[N:16]([C@@H:25]([CH:34]3[CH2:36][CH2:35]3)[CH2:26][NH:27][S:28]([CH:31]3[CH2:32][CH2:33]3)(=[O:30])=[O:29])[C:15](=[O:37])[C@:14]([CH2:38][C:39]([OH:47])=[O:40])([CH2:41][CH3:42])[CH2:13]2)[CH:9]=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 8028TetrahydrofuranHCID 23668197Sodium ChloriteHCID 86660737HCID 86660737, compound

Product 1

HCID 67999573HCID 67999573, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 516951Monobasic potassium phosphateSolvent2×

Procedure

A solution of sodium chlorite (58.9 mg, 0.651 mmol) in 0.25×1.25 M potassium phosphate monobasic in water (1 mL) at 0° C. was added to a clear solution of N—((S)-2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-ethyl-2-oxo-3-(2-oxoethyl)piperidin-1-yl)-2-cyclopropylethyl)cyclopropanesulfonamide (Example 254, Step C, 94 mg, 0.163 mmol) in 1.25 M potassium phosphate monobasic in water (1 mL)+t-butanol (1 mL)+2 M 2-methylbut-2-ene in THF (4.07 mL, 8.14 mmol). After stirring at ambient temperature for 4 hours, the reaction was quenched with 0.6 mL of 1 M sodium thiosulfate solution. After stirring for 10 min at ambient temperature, the mixture was acidified with 1.2 mL of 1 M potassium bisulphate solution. The mixture was extracted with ethyl acetate. The organic layer was washed with water then sat. aq. NaCl solution and dried over sodium sulfate. Purification by reverse phase HPLC (Sunfire Prep C18 OBD 10 μm column, gradient elution of 20% MeCN in water to 80% MeCN in water over a 30 min period, where both solvents contain 0.1% TFA) afforded the title compound.

Workup

  1. customthe reaction was quenched with 0.6 mL of 1 M sodium thiosulfate solution
  2. stirringAfter stirring for 10 min at ambient temperature
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with water
  5. dry with materialsat. aq. NaCl solution and dried over sodium sulfate
  6. customPurification by reverse phase HPLC (Sunfire Prep
  7. washC18 OBD 10 μm column, gradient elution of 20% MeCN in water to 80% MeCN in water over a 30 min period, where both solvents

Sources & evidence

ORD record
ord-3beccb64136f4e5fb2907ac56380b21c
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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