Potassium Carbonate → tert-butyl (2S)-4-(4-bromo-5-methyl-thiazol-2-yl)-2-isobutyl-piperazine-1-carboxylate

HRID 1044030Notes

Reaction equation

HRID 1044030 reaction equation
Br[C:2]1[S:3][C:4]([CH3:8])=[C:5]([Br:7])[N:6]=1.[C:9]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][C@@H:17]1[CH2:22][CH:23]([CH3:25])[CH3:24])([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O>[Br:7][C:5]1[N:6]=[C:2]([N:19]2[CH2:20][CH2:21][N:16]([C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[C@@H:17]([CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:18]2)[S:3][C:4]=1[CH3:8]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 17750437tert-Butyl (2S)-2-(2-methylpropyl)piperazine-1-carboxylateHCID 672125712,4-Dibromo-5-methyl-1,3-thiazole

Product 1

HCID 70371764tert-butyl (2S)-4-(4-bromo-5-methyl-thiazol-2-yl)-2-isobutyl-piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2,4-dibromo-5-methyl-thiazole (1.189 g, 3.563 mmol), (S)—N-Boc-2-isobutylpiperazine (863.5 mg, 3.563 mmol) and potassium carbonate (1.477 g, 10.69 mmol) in DMF (15 mL) were heated at 95° C. for 18 h. Cooled to rt, diluted with EtOAc, washed with water, brine, dried (MgSO4), filtered and concentrated in vacuo. Crude product purified by flash chromatography (40 g SiO2, 0 to 5% EtOAc/petrol) to leave impure product as a very pale orange sticky oil (930 mg, 49% based on 78.9% purity); 1H NMR DMSO-d6 δ 0.90 (t, 6H), 1.36-1.31 (br m, 2H), 1.42 (s, 9H), 1.46-1.42 (masked signal, 1H), 2.18 (s, 3H), 3.02-2.91 (m, 2H), 3.14 (dd, 1H), 3.60 (d, 1H), 3.78-3.68 (m, 1H), 3.86 (d, 1H), 4.19 (br s, 1H); ES+ 420.11.

Workup

  1. washwashed with water, brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customCrude product purified by flash chromatography (40 g SiO2, 0 to 5% EtOAc/petrol)
  6. customto leave impure product as a very pale orange sticky oil (930 mg, 49% based on 78.9% purity)

Sources & evidence

ORD record
ord-0711b58f2e124aa8a439220fdff167b9
Source dataset
uspto-grants-2013_10
Patent number
US08563576B2

Reaction notes

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