1,2-Dichloroethane → tert-butyl 2,4-dioxo-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridine-1-carboxylate

HRID 885902

Reaction equation

HRID 885902 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:13][CH2:12][CH2:11][CH:10]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.[CH3:21][C:22]1(C)OC(=O)CC(=O)[O:23]1.OS([O-])(=O)=O.[Na+]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[O:23]=[C:22]1[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH:9]2[CH2:13][CH2:12][CH2:11][CH:10]2[C:14](=[O:16])[CH2:21]1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 516919Sodium BisulfateHCID 35647322-((tert-Butoxycarbonyl)amino)cyclopentanecarboxylic acid

Product 1

HCID 86642118tert-butyl 2,4-dioxo-5,6,7,7a-tetrahydro-4aH-cyclopenta[b]pyridine-1-carboxylateYield 93.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2-[(tert-butoxycarbonyl)amino]cyclopentanecarboxylic acid (0.24 g, 1.06 mmol) in DCM (4.5 mL) was added EDC (0.31 g, 1.59 mmol), DMAP (0.19 g, 1.59 mmol) and Meldrum's acid (0.15 g, 1.06 mmol). After stirring for 18 h at r.t., the reaction mixture was poured into aqueous 1M NaHSO4 solution (5 mL) and extracted with DCM (3×20 mL). The combined organics were dried over MgSO4, filtered and concentrated in vacuo to give a clear yellow oil which was dissolved in EtOAc (5 mL) and heated to 80° C. for 18 h. The reaction mixture was then cooled and concentrated in vacuo to give the title compound (0.25 g, 42%) as a yellow solid that was used without further purification. δH (CDCl3) 4.64-4.55 (1H, m), 2.98-2.92 (1H, m), 2.37-2.20 (2H, m), 1.99-1.60 (6H, m), 1.58 (9H, s). LCMS (ES+) 198.0 ((M−tBu)+H)+.

Workup

  1. extractionextracted with DCM (3×20 mL)
  2. dry with materialThe combined organics were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a clear yellow oil which
  6. temperatureheated to 80° C. for 18 h
  7. temperatureThe reaction mixture was then cooled
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c5e322381b244f1188d9e42a010d8aaf
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Linked notes

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