Ethyl 8-oxa-1-azaspiro[4.5]decane-2-carboxylate → ethyl 1-{N-[(methyloxy)carbonyl]-L-valyl}-8-oxa-1-azaspiro[4.5]decane-2-carboxylate

HRID 454451Notes

Reaction equation

HRID 454451 reaction equation
[NH:1]1[C:5]2([CH2:10][CH2:9][O:8][CH2:7][CH2:6]2)[CH2:4][CH2:3][CH:2]1[C:11]([O:13][CH2:14][CH3:15])=[O:12].[CH3:16][O:17][C:18]([NH:20][C@H:21]([C:25](Cl)=[O:26])[CH:22]([CH3:24])[CH3:23])=[O:19]>ClCCl.[Ag]C#N>[CH3:16][O:17][C:18]([NH:20][C@H:21]([C:25]([N:1]1[C:5]2([CH2:6][CH2:7][O:8][CH2:9][CH2:10]2)[CH2:4][CH2:3][CH:2]1[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:26])[CH:22]([CH3:23])[CH3:24])=[O:19]

Participants

5

Reactant 2

HCID 58313084Ethyl 8-oxa-1-azaspiro[4.5]decane-2-carboxylateHCID 86654825Carbamic acid, N-[(1S)-1-(chlorocarbonyl)-2-methylpropyl]-, methyl ester

Product 1

HCID 58313069ethyl 1-{N-[(methyloxy)carbonyl]-L-valyl}-8-oxa-1-azaspiro[4.5]decane-2-carboxylateYield 20%

Reagents, catalysts & solvents 2

HCID 178509332CID 101611454CatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of ethyl 8-oxa-1-azaspiro[4.5]decane-2-carboxylate (166) (125 mg, 0.59 mmol) in anhydrous dichloromethane (2 mL) was added silver cyanide (98 mg, 0.73 mmol) followed by N-[(methyloxy)carbonyl]-L-valyl chloride (142 mg, 0.73 mmol) as a solution in anhydrous dichloromethane (3.5 mL) and the solution stirred at room temperature for 18 h under nitrogen. The reaction is filtered and treated with methanol and stirred for 5 minutes. The reaction is concentrated in vacuo and the residue purified by silica gel chromatography eluting with 30-100% hexanes/EtOAc to afford the title compound as a white solid (43 mg, 20% yield).

Workup

  1. filtrationThe reaction is filtered
  2. additiontreated with methanol
  3. stirringstirred for 5 minutes
  4. concentrationThe reaction is concentrated in vacuo
  5. customthe residue purified by silica gel chromatography
  6. washeluting with 30-100% hexanes/EtOAc

Sources & evidence

ORD record
ord-805a24d0c5f14d2895681b0c9973016f
Source dataset
uspto-grants-2013_07
Patent number
US08492554B2

Reaction notes

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