tert-Butyl piperazine-1-carboxylate → HCID 70975537, compound

HRID 875025Notes

Reaction equation

HRID 875025 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[S:22][CH:23]=[C:24]([CH:26]=O)[N:25]=2)=[CH:17][CH:16]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]2[S:22][CH:23]=[C:24]([CH2:26][N:4]3[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]3)[N:25]=2)=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 71319282-(4-Fluorophenyl)-1,3-thiazole-4-carbaldehyde

Product 1

HCID 70975537HCID 70975537, compoundYield 65.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

tert-Butyl piperazine-1-carboxylate (62 mg, 0.33 mmol) was added to a solution of 2-(4-fluorophenyl)thiazole-4-carbaldehyde (70 mg, 0.34 mmol) in 1,2-dichloroethane (3 mL) at 0° C., followed by sodium triacetoxyborohydride (85 mg, 0.4 mmol). The reaction mixture was allowed to warm up to room temperature, stirred for 16 h and further heated to 50° C. for another 4 h. The reaction mixture was quenched with 10% aqueous NaHCO3 and extracted with EtOAc. The combined extracts were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 35% EtOAc in petroleum ether) to afford tert-butyl 4-((2-(4-fluorophenyl)thiazol-4-yl)methyl)piperazine-1-carboxylate (82 mg, yield 64%). 1H NMR (300 MHz, CDCl3) δ 7.96-7.91 (dd, J=9.0 Hz, 5.3 Hz, 2H), 7.15-7.09 (m, 3H), 3.75 (s, 2H), 3.50-3.46 (m, 4H), 2.55-2.52 (m, 4H), 1.46 (s, 9H). MS (ESI) m/z: Calculated for C19H24FN3O2S: 377.16. found: 378.3 (M+H)+

Workup

  1. temperaturefurther heated to 50° C. for another 4 h
  2. customThe reaction mixture was quenched with 10% aqueous NaHCO3
  3. extractionextracted with EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 35% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-b8c004c9fff24359aea0649637b128c7
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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