Tetrahydrofuran → Bavisant

HRID 2246177Notes

Reaction equation

HRID 2246177 reaction equation
[CH:1]1([N:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12]C(C)(C)C)=O)[CH2:6][CH2:5]2)[CH2:3][CH2:2]1.[N:17]1([C:23](OC(C)(C)C)=O)[CH2:22][CH2:21]N[CH2:19][CH2:18]1.C(O[C:33]1(O[Si](C)(C)C)[CH2:35][CH2:34]1)C.[BH3-]C#N.[Na+].[OH-:45].[Na+].O1C[CH2:50][CH2:49][CH2:48]1>O.C(O)(=O)C.CO>[CH:1]1([N:4]2[CH2:5][CH2:6][N:7]([C:10]([C:34]3[CH:35]=[CH:33][C:50]([CH2:23][N:17]4[CH2:18][CH2:19][O:45][CH2:21][CH2:22]4)=[CH:49][CH:48]=3)=[O:12])[CH2:8][CH2:9]2)[CH2:2][CH2:3]1

Participants

10

Reactant 6

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 20294524tert-Butyl 4-cyclopropylpiperazine-1-carboxylate

Product 1

HCID 16061509BavisantYield 100%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl 4-cyclopropylpiperazine-1-carboxylate. A mixture of tert-butyl piperazine-1-carboxylate (75.0 g), tetrahydrofuran (THF) (500 mL), methanol (500 mL), [(1-ethoxycyclopropyl)oxy]trimethylsilane (161 mL), NaBH3CN (38.0 g), and acetic acid (37 mL) was heated at 60° C. for 5 h. The mixture was cooled to rt, treated with water (30 mL) and stirred for 5 min. The mixture was then treated with 1 N NaOH (130 mL) and was further stirred for 15 min. The mixture was concentrated, and the remaining aqueous solution was extracted with CH2Cl2 (500 mL). The organic layer was washed with 1 N NaOH (500 mL). The combined aqueous layers were extracted with CH2Cl2 (150 mL). The combined organic layers were washed with brine (400 mL), dried (Na2SO4), and concentrated to give the title compound as a white solid (92 g, 100%). MS (ESI): mass calcd. for C12H22N2O2, 226.17; m/z found, 227.2 [M+H+]. 1H NMR (400 MHz, CDCl3): 3.39 (t, J=5.0 Hz, 4H), 2.55 (t, J=4.9 Hz, 4H), 1.60 (ddd, J=10.3, 6.5, 3.8 Hz, 1H), 1.46 (s, 9H), 0.49-0.38 (m, 4H).

Workup

  1. temperatureThe mixture was cooled to rt
  2. stirringwas further stirred for 15 min
  3. concentrationThe mixture was concentrated
  4. extractionthe remaining aqueous solution was extracted with CH2Cl2 (500 mL)
  5. washThe organic layer was washed with 1 N NaOH (500 mL)
  6. extractionThe combined aqueous layers were extracted with CH2Cl2 (150 mL)
  7. washThe combined organic layers were washed with brine (400 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2fb4292f87d14a118d8f181f1df76089
Source dataset
uspto-grants-2010_03
Patent number
US07687499B2

Reaction notes

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