Tert-butyl 8-(2,2-difluoroethyl)-10-[methoxy(methyl)carbamoyl]-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate → Tert-butyl 8-(2,2-difluoroethyl)-10-propanoyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72883Notes

Reaction equation

HRID 72883 reaction equation
[F:1][CH:2]([F:28])[CH2:3][N:4]1[CH2:21][CH:20]([C:22](=[O:27])N(OC)C)[O:19][C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[CH2:5]1.[CH2:29]([Mg]Br)[CH3:30]>C1COCC1>[F:28][CH:2]([F:1])[CH2:3][N:4]1[CH2:21][CH:20]([C:22](=[O:27])[CH2:29][CH3:30])[O:19][C:6]2([CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][CH2:11]2)[CH2:5]1

Participants

4

Reactant 2

HCID 86672468Tert-butyl 8-(2,2-difluoroethyl)-10-[methoxy(methyl)carbamoyl]-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateHCID 178418443HCID 178418443, compound

Product 1

HCID 86672467Tert-butyl 8-(2,2-difluoroethyl)-10-propanoyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylateYield 83.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To tert-butyl 8-(2,2-difluoroethyl)-10-[methoxy(methyl)carbamoyl]-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (295 mg, 0.72 mmol) in THF (3 mL) at −78° C. under an atmosphere of nitrogen, was added ethylmagnesium bromide (1.7 mL of 1 M in THF, 1.7 mmol) dropwise. The reaction mixture was stirred at the same temperature for 0.5 hours, then at 0° C. for 1 hour. The reaction mixture was quenched with ethyl acetate (20 mL) and sat. aq. NaHCO3 (10 mL). The aqueous layer was further extracted with EtOAc (2×20 mL), and the combined organics were dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography (0-100% ethyl acetate/hexane) to give tert-butyl 8-(2,2-difluoroethyl)-10-propanoyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (227 mg, 83%) as a colorless oil. ESI-MS m/z calc. 376.2. Found 377.3 (M+1)+; Retention time: 1.76 minutes. 1H NMR (400 MHz, CDCl3) δ 6.01-5.70 (m, 1H), 4.21-4.15 (m, 1H), 3.91-3.75 (m, 2H), 3.33-3.22 (m, 1H), 3.15-2.98 (m, 2H), 2.79-2.57 (m, 5H), 2.43-2.35 (m, 1H), 2.19-2.06 (m, 2H), 1.61-1.39 (m, 12H), 1.06 (t, J=7.3 Hz, 3H).

Workup

  1. waitat 0° C. for 1 hour
  2. customThe reaction mixture was quenched with ethyl acetate (20 mL) and sat. aq. NaHCO3 (10 mL)
  3. extractionThe aqueous layer was further extracted with EtOAc (2×20 mL)
  4. dry with materialthe combined organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by silica gel column chromatography (0-100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4d03a08f53f44a09924655af919db26d
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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