Acetic Acid → 1-methyl-4-(1,4-dioxaspiro[4.5]decan-8-yl)piperazine

HRID 1924476Notes

Reaction equation

HRID 1924476 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[O:8]1[C:12]2([CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)[O:11][CH2:10][CH2:9]1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH:15]2[CH2:16][CH2:17][C:12]3([O:11][CH2:10][CH2:9][O:8]3)[CH2:13][CH2:14]2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 113794731-methyl-4-(1,4-dioxaspiro[4.5]decan-8-yl)piperazineYield 99.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-Methyl-piperazine (128.27 g, 105.90 ml, 1.28 mol) was added in one portion to a stirred and cooled (3° C.) solution of 1,4-dioxaspiro[4.5]decan-8-one (200.00 g, 1.28 mol) in 1,2-dichloroethane (2.0 L). Then glacial acetic acid (76.90 g, 73.31 ml, 1.28 mol) was added in one portion followed by solid NaBH(OAc)3 (379.97 g, 1.79 mol) portionwise over 20 min. The reaction was slowly allowed to warm to RT and was stirred overnight. The reaction was quenched by addition of 10% aqueous NaOH (3×450 mL) with stirring over a period of 25 min. An exotherm of ca. 10° C. was observed. The mixture was stirred for 30 min. The organic layer was separated. Aqueous layer was further extracted with CH2Cl2 (3×1 L). Brine (1000 mL) was added to the aqueous layer and extracted with EtOAc (2×1000 mL). The combined organic solutions were dried (MgSO4) and concentrated to afford 9 (305.00 g, 1.27 mol, 99.10% yield) as brown/orange oil. 1H NMR (400 MHz, CDCl3) δ 1.45-1.68 (m, 4H), 1.72-1.90 (m, 4H), 1.99 (s, 3H), 2.45 (s, 2H), 2.56-2.67 (m, 1H), 2.87 (bs, 6H), 3.86-3.95 (m, 4H).

Workup

  1. stirringwas stirred overnight
  2. customThe reaction was quenched by addition of 10% aqueous NaOH (3×450 mL)
  3. stirringwith stirring over a period of 25 min
  4. customAn exotherm of ca. 10° C.
  5. stirringThe mixture was stirred for 30 min
  6. customThe organic layer was separated
  7. extractionAqueous layer was further extracted with CH2Cl2 (3×1 L)
  8. additionBrine (1000 mL) was added to the aqueous layer
  9. extractionextracted with EtOAc (2×1000 mL)
  10. dry with materialThe combined organic solutions were dried (MgSO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-6ef899752e4a4fff92c841264ab2b11c
Source dataset
uspto-grants-2012_05
Patent number
US08178552B2

Reaction notes

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