Diisopropylethylamine → tert-Butyl 4-(4-methanesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)piperazine-1-carboxylate

HRID 1295559Notes

Reaction equation

HRID 1295559 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][CH2:9][N:8]([S:12]([CH3:15])(=[O:14])=[O:13])[C:7]=2[CH:16]=1.[N:17]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(N(CC)C(C)C)(C)C>CC(O)C>[CH3:15][S:12]([N:8]1[C:7]2[CH:16]=[C:3]([CH2:2][N:20]3[CH2:19][CH2:18][N:17]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:22][CH2:21]3)[CH:4]=[CH:5][C:6]=2[O:11][CH2:10][CH2:9]1)(=[O:14])=[O:13]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 694200776-Bromomethyl-4-methanesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazine

Product 1

HCID 86597571tert-Butyl 4-(4-methanesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)piperazine-1-carboxylateYield 71.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

6-Bromomethyl-4-methanesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazine (2.6 g, 8.5 mmol) and tert-butyl piperazine-1-carboxylate (1.58 g, 8.5 mmol) were treated with propan-2-ol (100 mL) followed by N,N-diisopropylethylamine (10.96 g, 85 mmol) and the resulting mixture heated at reflux for 72 h then evaporated to dryness under reduced pressure. The residue was partitioned between ethyl acetate and saturated NaHCO3 aq. and the phases separated. The organic phase was washed with water, saturated brine, dried (MgSO4) and evaporated to dryness under reduced pressure. Chromatography on SiO2, eluting with ethyl acetate in 60°–80° petroleum ether, gave the title compound (2.5 g, 71%) as a brown foam.

Workup

  1. temperaturethe resulting mixture heated
  2. temperatureat reflux for 72 h
  3. customthen evaporated to dryness under reduced pressure
  4. customThe residue was partitioned between ethyl acetate and saturated NaHCO3 aq.
  5. customthe phases separated
  6. washThe organic phase was washed with water, saturated brine
  7. dry with materialdried (MgSO4)
  8. customevaporated to dryness under reduced pressure
  9. washChromatography on SiO2, eluting with ethyl acetate in 60°–80° petroleum ether

Sources & evidence

ORD record
ord-2859919803cd427ea887c1b1fcc014f3
Source dataset
uspto-grants-2007_07
Patent number
US07244726B2

Reaction notes

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