Ammonium Chloride → (5S)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-3-yl]-4-propyl-5-methylmorpholin-2-ol
Reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][CH:10]=[C:9]2[CH3:14])=[N:6][CH:7]=1.C([Li])(C)(C)C.[CH2:20]([N:23]1[C@@H:28]([CH3:29])[CH2:27][O:26][C:25](=[O:30])[CH2:24]1)[CH2:21][CH3:22].[NH4+].[Cl-]>C1COCC1.C1(C)C=CC=CC=1>[CH3:14][C:9]1[N:8]([C:5]2[N:6]=[CH:7][C:2]([C:25]3([OH:30])[O:26][CH2:27][C@H:28]([CH3:29])[N:23]([CH2:20][CH2:21][CH3:22])[CH2:24]3)=[CH:3][CH:4]=2)[C:12]([CH3:13])=[CH:11][CH:10]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
5-bromo-2-(2,5-dimethyl-pyrrol-1-yl)-pyridine (1.5 g 5.9 mmol) was azeotroped with toluene and dissolved in THF (20 ml). This mixture was cooled to −78 C and t-butyllithium (1.7M in pentane, 7 ml, 11.9 mmol) was added maintaining the temperature below −70 C. The material from example 62 was dissolved in THF (20 ml) and added to the mixture immediately on completion of the t-butyllithium addition. The mixture was allowed to stir at −78° C. for 30 minutes at which time NH4Cl (10% aq, 150 ml) was added and the mixture extracted into EtOAc (200 ml), dried with magnesium sulphate, filtered and evaporated. Flash chromatography on SiO2 eluting with a stepped gradient from 25% EtOAc/pentane to 50% EtOAc/pentane gave the title compound as mixture of diastereoisomers in approximately 3.5:1 ratio as a yellow oil (480 mg).
Workup
- additionwas added
- temperaturemaintaining the temperature below −70 C
- additionwas added
- extractionthe mixture extracted into EtOAc (200 ml)
- dry with materialdried with magnesium sulphate
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-b12df79799854fdf82c5fc3634cf07f6
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07902188B2
Reaction notes
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