Tert-butyl 3-oxopiperazine-1-carboxylate → HCID 86586605, compound

HRID 1840584Notes

Reaction equation

HRID 1840584 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:15][CH2:14][C:11]3([O:13][CH2:12]3)[CH2:10][CH2:9]2)[CH:3]=1.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][NH:26][C:25](=[O:29])[CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].CC(C)([O-])C.[K+]>C(O)(C)(C)C>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][N:26]([CH2:12][C:11]2([OH:13])[CH2:14][CH2:15][N:8]([C:4]3[CH:3]=[C:2]([Cl:1])[N:7]=[CH:6][N:5]=3)[CH2:9][CH2:10]2)[C:25](=[O:29])[CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 23447336HCID 23447336, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 86586605HCID 86586605, compoundYield 76.6%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-(6-chloropyrimidine-4-yl)-1-oxa-6-azaspiro[2,5]octane (4.00 g) and 4-(tert-butoxycarbonyl)-2-piperazinone (3.38 g) in tert-butylalcohol (50 ml) was added potassium tert-butoxide (0.57 g), and the mixture was stirred at 80° C. overnight. The reaction solution was concentrated, and the residue was diluted with ethyl acetate (100 ml), washed with 0.5N hydrochloric acid and saturated brine, dried and concentrated. The residue was purified with silica gel column chromatography (eluent: ethyl acetate) and crystallized from a mixture of ethyl acetate and diethylether to give colorless crystals of 4-(tert-butoxycarbonyl)-1-[1-(6-chloro-4-pyrimidinyl)-4-hydroxypiperidin-4-ylmethyl]piperazin-2-one (5.51 g).

Workup

  1. concentrationThe reaction solution was concentrated
  2. additionthe residue was diluted with ethyl acetate (100 ml)
  3. washwashed with 0.5N hydrochloric acid and saturated brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel column chromatography (eluent: ethyl acetate)
  7. customcrystallized from a mixture of ethyl acetate and diethylether

Sources & evidence

ORD record
ord-63bd9e7e9f344921a7a7db7946648363
Source dataset
uspto-grants-2004_01
Patent number
US06680312B2

Reaction notes

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