Dimethyl Sulfoxide → 1,1-Dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-oxopropyl)-1-piperidinecarboxylate

HRID 489790Notes

Reaction equation

HRID 489790 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]([CH3:41])([CH3:40])[C:13]([NH:15][C:16]1[N:21]=[C:20]([F:22])[C:19]([CH:23]([OH:39])[CH2:24][CH2:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)=[CH:18][CH:17]=1)=[O:14].C(N(CC)CC)C>ClCCl>[CH3:11][C:12]([CH3:41])([CH3:40])[C:13]([NH:15][C:16]1[N:21]=[C:20]([F:22])[C:19]([C:23](=[O:39])[CH2:24][CH2:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)=[CH:18][CH:17]=1)=[O:14]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 222626141,1-Dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-hydroxypropyl)-1-piperidinecarboxylate

Product 1

HCID 222626761,1-Dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-oxopropyl)-1-piperidinecarboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of oxalyl chloride (0.11 ml, 1.25 mmol) in dichloromethane (10 ml) was added dropwise dimethylsulfoxide (0.18 ml, 2.51 mmol) at −78° C. After stirring for 10 min, a solution of 1,1-dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-hydroxypropyl)-1-piperidinecarboxylate (step 1, 500 mg, 1.14 mmol) in dichloromethane (5 ml) was added to the mixture at −78° C. After 15 min, triethylamine (0.79 ml, 5.70 mmol) was added at the same temperature and the resulting mixture was allowed to warm up to room temperature and stirred for 18 h. The mixture was quenched with 1N aqueous hydrochloric acid (100 ml) and extracted with dichloromethane (150 ml). The organic layer was washed with water (50 ml) and dried over magnesium sulfate. Removal of solvent gave a pale yellow solid, which was chromatographed on a column of silica gel eluting with ethyl acetate/hexane (4:1 ) to afford 362 mg (73%) of the title compound as a white solid.

Workup

  1. waitAfter 15 min
  2. stirringstirred for 18 h
  3. customThe mixture was quenched with 1N aqueous hydrochloric acid (100 ml)
  4. extractionextracted with dichloromethane (150 ml)
  5. washThe organic layer was washed with water (50 ml)
  6. dry with materialdried over magnesium sulfate
  7. customRemoval of solvent
  8. customgave a pale yellow solid, which
  9. customwas chromatographed on a column of silica gel eluting with ethyl acetate/hexane (4:1 )

Sources & evidence

ORD record
ord-f08ad051933f4437a77e641b3bed07b2
Source dataset
uspto-grants-2005_12
Patent number
US06979690B2

Reaction notes

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