Isopropyl iodide → HCID 9889584, compound

HRID 2119378Notes

Reaction equation

HRID 2119378 reaction equation
[H-].[Na+].[CH3:3][C@H:4]1[CH2:9][CH2:8][CH2:7][C@@H:6]([CH3:10])[N:5]1[CH2:11][CH2:12][NH:13][C:14]([C@@H:16]1[CH2:21][CH2:20][CH2:19][CH2:18][N:17]1[C:22]1[O:23][C:24]2[CH:30]=[C:29]([OH:31])[CH:28]=[CH:27][C:25]=2[N:26]=1)=[O:15].I[CH:33]([CH3:35])[CH3:34]>CN(C)C=O>[CH3:10][C@H:6]1[CH2:7][CH2:8][CH2:9][C@@H:4]([CH3:3])[N:5]1[CH2:11][CH2:12][NH:13][C:14]([C@@H:16]1[CH2:21][CH2:20][CH2:19][CH2:18][N:17]1[C:22]1[O:23][C:24]2[CH:30]=[C:29]([O:31][CH:33]([CH3:35])[CH3:34])[CH:28]=[CH:27][C:25]=2[N:26]=1)=[O:15]

Participants

5

Reactant 3

HCID 6362Isopropyl iodide2×HCID 24758Sodium hydride2×HCID 9887247HCID 9887247, compound

Product 1

HCID 9889584HCID 9889584, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride as a 60% dispersion in oil (6 mg) was added to a solution of (2S)-N-2-[(cis)-2,6-dimethyl-1-piperidinyl]ethyl-1-(6-hydroxy-1,3-benzoxazol-2-yl)-2-piperidinecarboxamide (54.5 mg) [see Preparation 39] in dimethylformamide (2 ml) at 0° C. After 5 minutes 2-iodopropane (0.014 ml) were added. The reaction mixture was stirred at room temperature for 4 hours, after which time sodium hydride (3 mg) followed by 2-iodopropane (0.007 ml) was added. The mixture was stirred for a further 18 hours, after which time the solvent was removed and the residue partitioned between water and diethyl ether. The organic layer was separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent system of 97:3.5:0.5, by volume, dichloromethane/methanol/0.88 aqueous ammonia solution to afford (2S)-N-2-[(cis)-2,6-dimethyl-1-piperidinyl]ethyl-1-(6-isopropoxy-1,3-benzoxazol-2-yl)-2-piperidinecarboxamide (24 mg) as a brown solid.

Workup

  1. additionwas added
  2. stirringThe mixture was stirred for a further 18 hours
  3. customafter which time the solvent was removed
  4. customthe residue partitioned between water and diethyl ether
  5. customThe organic layer was separated
  6. dry with materialdried over magnesium sulphate
  7. customthe solvent removed under reduced pressure
  8. customThe crude product was purified by column chromatography on silica gel eluting with a solvent system of 97:3.5:0.5, by volume, dichloromethane/methanol/0.88 aqueous ammonia solution

Sources & evidence

ORD record
ord-3f004489de604fd6b4727f9624e4e032
Source dataset
uspto-grants-2004_02
Patent number
US06686357B1

Reaction notes

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