HCID 49858028, compound → HCID 49858030, compound
Reaction equation
[N:1]([C@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([F:14])[CH:12]=2)[O:7][C:6]([CH2:17][F:18])([CH2:15][F:16])[CH2:5]1)=[N+]=[N-]>CO.[Pd]>[F:14][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[O:7][C:6]([CH2:15][F:16])([CH2:17][F:18])[CH2:5][C@H:4]2[NH2:1]Participants
Reactant 1
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 50 °C
Procedure
A solution of Example 65B (54.1 mmol) in THF (190 mL) was cooled to <5° C. To this solution was added 1,8-diazabicyclo[5.4.0]undec-7-ene (12.1 mL, 81.0 mmol) followed by diphenylphosphoryl azide (15.2 mL, 70.3 mmol), keeping the temperature≦5° C. (no exotherm). After stirring for 2 hours at ≦5° C., the reaction mixture was warmed to ambient temperature and stirred for 14 hours. The reaction mixture was diluted with MTBE (250 mL), washed with 2N NaOH (2×125 mL), brine (50 mL), 2N HCl (2×125 mL), and brine (50 mL). The organic portion was dried (Na2SO4), filtered, and concentrated, giving (R)-4-azido-6-fluoro-2,2-bis(fluoromethyl)chroman (14.6 g, >100%) as a dark oil. The crude (R)-4-azido-6-fluoro-2,2-bis(fluoromethyl)chroman in MeOH (300 mL) was added to 5% Pd—C (4.38 g) in a 500 mL stainless steel pressure bottle. The mixture was stirred for 3 hours at 50° C. and 30 psi H2. Upon cooling, the reaction mixture was filtered through a nylon membrane and concentrated. The resulting residue was used without further purification. MS (DCI) m/z 232 (M+H)+.
Workup
- temperatureUpon cooling
- filtrationthe reaction mixture was filtered through a nylon membrane
- concentrationconcentrated
- customThe resulting residue was used without further purification
Sources & evidence
- ORD record
- ord-fdfa7356013f49d993995c176bb1f0cb
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08604053B2
Reaction notes
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