Acetic Acid → Bavisant

HRID 604258Notes

Reaction equation

HRID 604258 reaction equation
[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[O:15])=[CH:10][CH:9]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(O[C:25]1(O[Si](C)(C)C)[CH2:27][CH2:26]1)C.C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[CH:25]1([N:19]2[CH2:18][CH2:17][N:16]([C:14]([C:11]3[CH:10]=[CH:9][C:8]([CH2:7][N:1]4[CH2:2][CH2:3][O:4][CH2:5][CH2:6]4)=[CH:13][CH:12]=3)=[O:15])[CH2:21][CH2:20]2)[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 59218186(4-Morpholin-4-ylmethyl-phenyl)piperazin-1-yl-methanone

Product 1

HCID 16061509BavisantYield 38%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of (4-morpholin-4-ylmethyl-phenyl)-piperazin-1-yl -methanone (0.128 g) in methanol (7.5 mL) was treated with (1-ethoxy-cyclopropoxy) -trimethyl-silane (1.5 mL), acetic acid (0.2 mL), and NaBH3CN (˜400 mg). The mixture was heated at 60° C. for 18 h, and then was cooled to rt and concentrated. The residue was diluted with 1 N NaOH and extracted with CH2Cl2. The organic layer was dried (Na2SO4) and concentrated. The residue was purified by column chromatography (SiO2) to give the title compound (0.0548 g, 38%). MS (ESI): mass calcd. for C19H27N3O2, 329.21; m/z found, 330.4 [M+H]+. 1H NMR (CDCl3): 7.36 (s, 4H), 3.79-3.68 (m, 6H), 3.50 (s, 2H), 3.44-3.32 (m, 2H), 2.74-2.61 (m, 2H), 2.60-2.50 (s, 2H), 2.45-2.40 (m, 4H), 1.66-1.62 (m, 1H), 0.49-0.44 (m, 2H), 0.44-0.39 (m, 2H).

Workup

  1. temperaturewas cooled to rt
  2. concentrationconcentrated
  3. additionThe residue was diluted with 1 N NaOH
  4. extractionextracted with CH2Cl2
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (SiO2)

Sources & evidence

ORD record
ord-ec8e6354af224ac79c17ebd39c0962da
Source dataset
uspto-grants-2011_03
Patent number
US07910582B2

Reaction notes

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