Potassium Carbonate → Tert-butyl 8-but-2-ynyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72904Notes

Reaction equation

HRID 72904 reaction equation
[OH:1][CH2:2][CH:3]1[O:20][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][NH:5][CH2:4]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:28][C:29]#[C:30][CH3:31]>CN(C)C=O.C(OCC)(=O)C>[C:16]([O:15][C:13]([N:10]1[CH2:9][CH2:8][C:7]2([O:20][CH:3]([CH2:2][OH:1])[CH2:4][N:5]([CH2:28][C:29]#[C:30][CH3:31])[CH2:6]2)[CH2:12][CH2:11]1)=[O:14])([CH3:17])([CH3:19])[CH3:18]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27568621-Bromo-2-butyneHCID 70872648Tert-butyl 10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 70872782Tert-butyl 8-but-2-ynyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 70.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

Tert-butyl 10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (1.35 g, 4.71 mmol), K2CO3 (3.26 g, 23.6 mmol) and 1-bromobut-2-yne (495 μL, 5.66 mmol) were combined in N,N-dimethylformamide (15 mL) and heated for 48 h at 45° C. under nitrogen. The reaction mixture was diluted with ethyl acetate (150 mL) and filtered. The filtrate was washed with water, 50% saturated sodium bicarbonate solution, and brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The desired fractions obtained from silica gel chromatography (5-20% methanol/dichloromethane) were combined and concentrated, then brought up in ethyl acetate, filtered and concentrated in vacuo to provide tert-butyl-8-but-2-ynyl-10-(hydroxymethyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (1.12 g, 3.31 mmol, 70%). ESI-MS m/z calc. 338.2. Found 339.3 (M+1)+; Retention time: 0.86 minutes (3 min run).

Workup

  1. filtrationfiltered
  2. washThe filtrate was washed with water, 50% saturated sodium bicarbonate solution, and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe desired fractions obtained from silica gel chromatography (5-20% methanol/dichloromethane)
  7. concentrationconcentrated
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-695ed6e6234a4a3d924861f7bc76eb45
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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