2-Methyl-2-butene → HCID 58573534, compound

HRID 1048367Notes

Reaction equation

HRID 1048367 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][N:15]=3)[N:12]([C@@H:21]([CH2:29][CH3:30])[CH2:22][N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:11](=[O:31])[C@:10]([CH2:33][CH:34]=[O:35])([CH3:32])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.CC(=CC)C.Cl([O-])=[O:42].[Na+].O.O.P([O-])(O)(O)=O.[Na+]>CC(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][N:15]=3)[N:12]([C@@H:21]([CH2:29][CH3:30])[CH2:22][N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:11](=[O:31])[C@:10]([CH2:33][C:34]([OH:42])=[O:35])([CH3:32])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23673460Sodium Phosphate, Monobasic, DihydrateHCID 58573346HCID 58573346, compound

Product 1

HCID 58573534HCID 58573534, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

To a solution of 16 mg (0.03 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-3-methyl-1-((S)-1-morpholinobutan-2-yl)-2-oxopiperidin-3-yl)acetaldehyde (Example 121, Step O) and 1.0 mL (9.4 mmol) of 2-methyl-2-butene in t-BuOH (3 mL) was added a solution of 28 mg (0.31 mmol) of sodium chlorite and 4.6 mg (0.03 mmol) of sodium dihydrogenphosphate dihydrate in water (1.6 mL). The resulting mixture was stirred at room temperature for 2 h, and then was quenched with 1 M HCl and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by reversed phase prep. HPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 35% MeCN in water to 60% MeCN in water over a 35 min period, where both solvents contain 0.1% TFA provided the title compound as a white solid.

Workup

  1. customwas quenched with 1 M HCl
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customPurification of the residue by reversed phase prep
  7. washHPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 35% MeCN in water to 60% MeCN in water over a 35 min period, where both solvents

Sources & evidence

ORD record
ord-0491b493f20f4962946fd03252bed844
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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