Propargyl bromide → (8R)-8-(3,5-Difluorophenyl)-8-methyl-9-prop-2-yn-1-yl-6,9-diazaspiro[4.5]decan-10-one
Reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([C@@:11]2([CH3:22])[NH:20][C:19](=[O:21])[C:14]3([CH2:18][CH2:17][CH2:16][CH2:15]3)[NH:13][CH2:12]2)[CH:7]=[C:8]([F:10])[CH:9]=1.[CH2:23](Br)[C:24]#[CH:25]>CN(C=O)C>[F:3][C:4]1[CH:5]=[C:6]([C@@:11]2([CH3:22])[N:20]([CH2:25][C:24]#[CH:23])[C:19](=[O:21])[C:14]3([CH2:15][CH2:16][CH2:17][CH2:18]3)[NH:13][CH2:12]2)[CH:7]=[C:8]([F:10])[CH:9]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Sodium hydride (86.0 mg, 2.15 mmol, 60% dispersion in mineral oil) was added to a solution of (8R)-8-(3,5-difluorophenyl)-8-methyl-6,9-diazaspiro[4.5]decan-10-one (502 mg, 1.791 mmol, described in Intermediate 1) in 5 ml of DMF. When the gas evolution had ceased, propargyl bromide (320 mg, 2.15 mmol, 80 wt % in toluene) was added to the solution at ambient temperature. After 16 hours, the reaction was quenched with water (20 mL) and extracted with CH2Cl2 (3×20 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified on silica gel, eluting with a gradient of CH2Cl2:ethyl acetate—98:2 to 50:50. The clean fractions were concentrated in vacuo to yield the title compound. MS: m/z=319 (M+1).
Workup
- customthe reaction was quenched with water (20 mL)
- extractionextracted with CH2Cl2 (3×20 ml)
- dry with materialThe combined organic layers were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product was purified on silica gel
- washeluting with a gradient of CH2Cl2
- concentrationThe clean fractions were concentrated in vacuo
Sources & evidence
- ORD record
- ord-d9bd9376dde54a9db14df114df109450
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08765759B2
Reaction notes
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