Triphenylphosphine → 2-Chloro-3-bromo-5-(1-t-butoxycarbonyl 3-(R)-pyrrolidinyloxy)-pyridine
Reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O.[C:32]([O:36][C:37]([N:39]1[CH2:43][CH2:42][C@@H:41]([OH:44])[CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].[Cl:45][C:46]1[C:51]([Br:52])=[CH:50][C:49](O)=[CH:48][N:47]=1>C1COCC1>[Cl:45][C:46]1[C:51]([Br:52])=[CH:50][C:49]([O:44][C@@H:41]2[CH2:42][CH2:43][N:39]([C:37]([O:36][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:38])[CH2:40]2)=[CH:48][N:47]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -20 °C
Procedure
To 3.15 gm (12 mmol) of PPh3 in 100 mL of dry THF at −20° C. was added 1.89 mL (12 mmol) of DEAD dropwise. The solution was allowed to stir 10 min. at −20° C. After 10 min, a solution containing 1.87 gm (10 mmol) of 1-t-butoxycarbonyl-3-(R)-hydroxypyrrolidine in 20 mL of dry THF was added dropwise. The solution was again allowed to stir 10 min at −20° C. After 10 min, to the solution was added 2.08 gm (10 mmol) of 2-chloro-3-bromo-5-hydroxypyridine at once. The solution was allowed to stir at room temperature overnight. Next day, solvent was removed under reduced pressure. The crude product was purified by flash chromatography (3:1, hexane:ethyl acetate) to obtain 3.65 gm (65%) of a foamy residue: 1H NMR (300 MHz, CD3OD) δ8.05 (1H, d, J=2.5 Hz), 7.78 (1H, d, J=2.5 Hz), 5.09 (1H, s), 3.66-3.32 (4H, m), 2.18 (2H, m), 1.46 (9H, s).
Workup
- waitAfter 10 min
- additionwas added dropwise
- stirringto stir 10 min at −20° C
- waitAfter 10 min
- stirringto stir at room temperature overnight
- customNext day, solvent was removed under reduced pressure
- customThe crude product was purified by flash chromatography (3:1, hexane:ethyl acetate)
Sources & evidence
- ORD record
- ord-9cb61caa6e4d44b29345ea9907973300
- Source dataset
- uspto-grants-2003_05
- Patent number
- US06562847B1
Reaction notes
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