Triethylamine → Tert-butyl 4-[(4-bromo-2-methylphenyl)methyl]piperazine-1-carboxylate

HRID 2278273Notes

Reaction equation

HRID 2278273 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([CH3:10])[CH:3]=1.[N:11]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:14]2[CH2:13][CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15]2)=[C:4]([CH3:10])[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 135551504-Bromo-2-methylbenzaldehyde

Product 1

HCID 89676989Tert-butyl 4-[(4-bromo-2-methylphenyl)methyl]piperazine-1-carboxylateYield 67.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A 500 mL round-bottom flask was charged with 4-bromo-2-methylbenzaldehyde (8.00 g, 40.2 mmol, 1.00 equiv), tert-butyl piperazine-1-carboxylate (9.40 g, 50.5 mmol, 1.26 equiv), triethylamine (6.50 g, 64.2 mmol, 1.60 equiv) and dichloroethane (200 mL). The resulting solution was stirred for 30 min at room temperature. Solid sodium triacetoxyborohydride (27.0 g, 127 mmol, 3.17 equiv) was added. The resulting solution was stirred overnight at room temperature. The reaction progress was monitored by LCMS. The reaction was then quenched by the addition of water (100 mL). The resulting solution was extracted with dichloromethane (3×200 mL) and the organic layers were combined, washed with brine (2×200 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (2/3) to yield 10.0 g (67% yield) of tert-butyl 4-[(4-bromo-2-methylphenyl)methyl]piperazine-1-carboxylate as a white solid. LCMS (ESI, m/z): 369 [M+H]+.

Workup

  1. stirringThe resulting solution was stirred overnight at room temperature
  2. customThe reaction was then quenched by the addition of water (100 mL)
  3. extractionThe resulting solution was extracted with dichloromethane (3×200 mL)
  4. washwashed with brine (2×200 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (2/3)

Sources & evidence

ORD record
ord-ac8bfc0749404f399082f6564bdff0c8
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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