Iodine → 4-{4-[4-(2,4-Dimethoxy-benzylcarbamoyl)-2-iodo-oxazol-5-yl]-phenyl}-2,2-dimethyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 2278385Notes

Reaction equation

HRID 2278385 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[O:24][CH:23]=[N:22][C:21]=3[C:25](=[O:38])[NH:26][CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=3[O:36][CH3:37])=[CH:16][CH:15]=2)[CH2:10][C:9]1([CH3:40])[CH3:39])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[I:51]I>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[O:24][C:23]([I:51])=[N:22][C:21]=3[C:25](=[O:38])[NH:26][CH2:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][C:29]=3[O:36][CH3:37])=[CH:16][CH:15]=2)[CH2:10][C:9]1([CH3:40])[CH3:39])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 807IodineHCID 2733832Lithium HexamethyldisilazideHCID 897392824-{4-[4-(2,4-Dimethoxy-benzylcarbamoyl)-oxazol-5-yl]-phenyl}-2,2-dimethyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 1183620374-{4-[4-(2,4-Dimethoxy-benzylcarbamoyl)-2-iodo-oxazol-5-yl]-phenyl}-2,2-dimethyl-piperazine-1-carboxylic acid tert-butyl esterYield 75.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-{4-[4-(2,4-dimethoxy-benzylcarbamoyl)-oxazol-5-yl]-phenyl}-2,2-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (2.6 g, 4.7 mmol) in 20 mL THF at −78° C. was added a 1M solution of LiHMDS (44 mL, 44 mmol) in THF. The mixture stirred for 0.5 h, then I2 (9 g, 35 mmol) was added in portions. The mixture was stirred at room temperature for 1 h. The mixture was quenched with 15% aqueous Na2S2O3 and extracted with EtOAc and washed with water. The organic phase was dried over Na2SO4. The solvent was removed in vacuo to give the crude product which was purified by silica gel column chromatography (PE/EtOAc=2/1 to PE/EtOAc/DCM=1/1/2) to afford the title compound (2.4 g, yield: 75%).

Workup

  1. stirringThe mixture was stirred at room temperature for 1 h
  2. customThe mixture was quenched with 15% aqueous Na2S2O3
  3. extractionextracted with EtOAc
  4. washwashed with water
  5. dry with materialThe organic phase was dried over Na2SO4
  6. customThe solvent was removed in vacuo
  7. customto give the crude product which
  8. customwas purified by silica gel column chromatography (PE/EtOAc=2/1 to PE/EtOAc/DCM=1/1/2)

Sources & evidence

ORD record
ord-e8e8f2194daa412d97ab706e95cc38b5
Source dataset
uspto-grants-2015_09
Patent number
US09133180B2

Reaction notes

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