HCID 88924281, compound → HCID 86672459, compound

HRID 712958Notes

Reaction equation

HRID 712958 reaction equation
[F:1][CH:2]([F:30])[CH2:3][N:4]1[CH2:9][C:8]2([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[O:7][CH:6]([C:22](=O)[NH:23][CH2:24][C:25](=[O:28])[CH2:26][CH3:27])[CH2:5]1>C1COCC1>[F:30][CH:2]([F:1])[CH2:3][N:4]1[CH2:9][C:8]2([CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH2:14]2)[O:7][CH:6]([C:22]2[O:28][C:25]([CH2:26][CH3:27])=[CH:24][N:23]=2)[CH2:5]1

Participants

3

Reactant 1

HCID 88924281HCID 88924281, compound

Product 1

HCID 86672459HCID 86672459, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

To tert-butyl 4-(2,2-difluoroethyl)-2-((2-oxobutyl)carbamoyl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (200 mg, 0.46 mmol) in THF (2 mL) was added Burgess' salt (275 mg, 1.15 mmol) and the reaction mixture was heated at 75° C. under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and partitioned between EtOAc and saturated aq. NaHCO3. The layers were separated and the aqueous layer was extracted once more with EtOAc. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give an orange oil. The residue was purified by silica gel column chromatography using 0-20% EtOAc in DCM as eluent to yield tert-butyl 4-(2,2-difluoroethyl)-2-(5-ethyloxazol-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate (160 mg, 84%) as a colorless oil. ESI-MS m/z calc. 415.2. found 416.5 (M+1)+; Retention time: 2.06 minutes (3 min run); 1H NMR (400 MHz, CDCl3) δ 6.69 (s, 1H), 6.06-5.68 (m, 1H), 4.89 (dd, J=10.7, 2.5 Hz, 1H), 3.85-3.58 (m, 2H), 3.37-3.01 (m, 3H), 2.87-2.59 (m, 6H), 2.45 (d, J=13.6 Hz, 1H), 2.30 (d, J=11.3 Hz, 1H), 1.65-1.48 (m, 3H), 1.45 (s, 9H), 1.25 (t, J=7.6 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and saturated aq. NaHCO3
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted once more with EtOAc
  5. dry with materialThe combined organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give an orange oil
  9. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7c19798b8e464e27971629d653c22430
Source dataset
uspto-grants-2015_11
Patent number
US09181273B2

Reaction notes

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