Triethylamine → 1-(1,4-Dioxaspiro[4,5]dec-8-ylacetyl)-4-(2-pyridinyl)piperazine

HRID 1600678Notes

Reaction equation

HRID 1600678 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([CH2:11][C:12]([OH:14])=O)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[N:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1>C(Cl)Cl>[O:4]1[C:5]2([CH2:6][CH2:7][CH:8]([CH2:11][C:12]([N:39]3[CH2:40][CH2:41][N:36]([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][N:30]=4)[CH2:37][CH2:38]3)=[O:14])[CH2:9][CH2:10]2)[O:1][CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 944591-(2-Pyridyl)piperazineHCID 151011212-(1,4-Dioxaspiro(4.5)decan-8-yl)acetic acid

Product 1

HCID 151011221-(1,4-Dioxaspiro[4,5]dec-8-ylacetyl)-4-(2-pyridinyl)piperazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (1,4-Dioxaspiro[4.5]dec-8-yl)-acetic acid (U.S. Pat. No. 5,124,332) (20.0 g, 99.8 mmol) and triethylamine (21 mL, 149 mmol) in 200 mL of methylene chloride (CH2Cl2) was cooled to 0° C. in an ice bath and treated with isobutyl chloroformate (13.98 mL, 107.8 mmol). After stirring for 10 minutes 1-(2-pyridinyl)piperazine (17.6 g, 108 mmol) is added in 50 mL of methylene chloride. The reaction is removed from the ice bath and stirred at room temperature for 24 hours. The reaction mixture is treated with 200 mL of a saturated sodium bicarbonate solution. The aqueous layer is separated and extracted with an additional 150 mL of methylene chloride. The combined organic fractions are dried over magnesium sulfate (MgSO4), and the solvent is removed under reduced pressure to give an oil which is triturated with diethyl ether (Et2O) to give 2-(1,4-dioxaspiro[4.5]dec-8-yl)-1-[4-(2-pyridinyl)-1-piperazinyl]-ethanone (22.7 g) as a white solid.

Workup

  1. customThe reaction is removed from the ice bath
  2. additionThe reaction mixture is treated with 200 mL of a saturated sodium bicarbonate solution
  3. customThe aqueous layer is separated
  4. extractionextracted with an additional 150 mL of methylene chloride
  5. dry with materialThe combined organic fractions are dried over magnesium sulfate (MgSO4)
  6. customthe solvent is removed under reduced pressure
  7. customto give an oil which
  8. customis triturated with diethyl ether (Et2O)

Sources & evidence

ORD record
ord-f184a5c307164f27920676071300a074
Source dataset
uspto-grants-1999_11
Patent number
US05977110

Reaction notes

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