Sodium hydride → HCID 67527759, compound

HRID 12373Notes

Reaction equation

HRID 12373 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:28][CH2:27][C:13]2([N:17]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[NH:16][C:15](=[O:26])[CH2:14]2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH2:29]([O:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38]Br)=[CH:36][CH:35]=1)[CH:30]([CH3:32])[CH3:31]>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:28][CH2:27][C:13]2([N:17]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[N:16]([CH2:38][C:37]3[CH:40]=[CH:41][C:34]([O:33][CH2:29][CH:30]([CH3:32])[CH3:31])=[CH:35][CH:36]=3)[C:15](=[O:26])[CH2:14]2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 22386652HCID 22386652, compoundHCID 57458016HCID 57458016, compound

Product 1

HCID 67527759HCID 67527759, compoundYield 50.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

NaH (24 mg, 0.50 mmol) was added slowly to a solution of 84AF84-19 (0.149 g, 0.41 mmol) in dry DMF (5 mL) and the mixture stirred at rt for 30 min. A solution of 4-isobutoxybenzyl bromide 69NLS69 (117 mg, 0.48 mmol) in dry DMF (1 mL) was added dropwise to the mixture. After 1 h stirring at rt the mixture was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulphate, filtered and concentrated in vacuo. Purification of the residue by column chromatography on silica gel, eluting with a stepwise gradient of 3-6% methanol in dichloromethane, followed by preparative reversed phase HPLC (C18) afforded the desired compound (109 mg, 50%).

Workup

  1. stirringAfter 1 h stirring at rt the mixture
  2. customwas partitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by column chromatography on silica gel
  7. washeluting with a stepwise gradient of 3-6% methanol in dichloromethane

Sources & evidence

ORD record
ord-52db395872194545a29f7d1756c837d4
Source dataset
uspto-grants-2010_06
Patent number
US07727999B2

Reaction notes

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