Tetrahydrofuran → Tert-butyl 8-but-2-ynyl-10,10-difluoro-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72909Notes

Reaction equation

HRID 72909 reaction equation
CSC.B.[F:5][C:6]1([F:25])[O:23][C:10]2([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH2:9][NH:8][C:7]1=O.CN(C)CCN.O1[CH2:36][CH2:35][CH2:34][CH2:33]1>>[CH2:33]([N:8]1[CH2:7][C:6]([F:25])([F:5])[O:23][C:10]2([CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]2)[CH2:9]1)[C:34]#[C:35][CH3:36]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 66053N,N-DimethylethylenediamineHCID 12423031(Dimethyl sulfide)trihydroboronHCID 57989103tert-Butyl 2,2-difluoro-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Product 1

HCID 70872876Tert-butyl 8-but-2-ynyl-10,10-difluoro-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Conditions

Temperature
55 °C

Procedure

Borane dimethylsulfide (36.3 μL, 0.408 mmol) was added dropwise to a solution of tert-butyl 10,10-difluoro-9-oxo-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (125 mg, 0.408 mmol) in tetrahydrofuran (3 mL). The reaction mixture was heated at 55° C. for 2 h then cooled to room temperature. The mixture was quenched with the careful dropwise addition of methanol (˜2 mL). N,N-dimethylethane-1,2-diamine (33.3 μL, 0.313 mmol) was then added and the mixture heated at 70° C. for 40 min. The reaction was concentrated, and silica gel chromatography (4 g silica, 1% triethylamine/4% methanol/dichloromethane)) provided tert-butyl 8-but-2-ynyl-10,10-difluoro-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate which was taken directly to the next reaction.

Workup

  1. temperaturethen cooled to room temperature
  2. customThe mixture was quenched with the careful dropwise addition of methanol (˜2 mL)
  3. temperaturethe mixture heated at 70° C. for 40 min
  4. concentrationThe reaction was concentrated

Sources & evidence

ORD record
ord-9acfb2ec7f894becb303ce89e2c64b64
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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