1,2-Dichloroethane → Tert-butyl 6,8-dioxo-5-azaspiro[3.5]nonane-5-carboxylate

HRID 1175121Notes

Reaction equation

HRID 1175121 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([CH2:13][C:14]([OH:16])=O)[CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.[CH3:21][C:22]1(C)OC(=O)CC(=O)[O:23]1.Cl.O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C:22](=[O:23])[CH2:21][C:14](=[O:16])[CH2:13][C:9]21[CH2:10][CH2:11][CH2:12]2)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 10751878(1-Aminocyclobut-1-yl)acetic acid, N-BOC protectedHCID 21885828Hydrate;hydrochloride

Product 1

HCID 59558334Tert-butyl 6,8-dioxo-5-azaspiro[3.5]nonane-5-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(1-tert-Butoxycarbonylamino-cyclobutyl)-acetic acid (6 g; 26 mmol) (Eur.J.Med.Chem. 34 (1999) 363), EDC (7.5 g; 39 mmol) DMAP (4.8 g; 39 mmol) and Meldrum's acid (3.77 g; 26 mmol) in CH2Cl2 (120 ml) are stirred at room temperature over night and poured on 2N HCl/water (40 ml/400 ml). The aqueous phase is extracted with CH2Cl2 twice, the organic phases are combined and dried over Na2SO4 and evaporated to dryness. The orange-colored residue is taken up in ethyl acetate (200 ml) and refluxed for 2.5 hours, diluted with hexanes (600 ml) and purified via chromatography (SiO2; Hexanes/acetone 92:8) yielding the title compound as yellowish crystals in a modest purity, which is sufficient to perform the next steps.

Workup

  1. extractionThe aqueous phase is extracted with CH2Cl2 twice
  2. dry with materialdried over Na2SO4
  3. customevaporated to dryness
  4. temperaturerefluxed for 2.5 hours
  5. additiondiluted with hexanes (600 ml)
  6. custompurified via chromatography (SiO2; Hexanes/acetone 92:8)

Sources & evidence

ORD record
ord-ccfcf49d365942e0be98591af4459599
Source dataset
uspto-grants-2010_11
Patent number
US07838674B2

Reaction notes

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