Ammonium Chloride → {5-Cyclopropyl-6-[(4-methoxybenzyl)oxy]pyridin-2-yl}[4-(cyclopropylsulfanyl)phenyl]methanol

HRID 70714Notes

Reaction equation

HRID 70714 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8][CH:9]2[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.C([Li])CCC.[CH:17]1([C:20]2[CH:21]=[CH:22][C:23]([CH:36]=[O:37])=[N:24][C:25]=2[O:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH2:19][CH2:18]1.[Cl-].[NH4+]>O1CCCC1>[CH:17]1([C:20]2[CH:21]=[CH:22][C:23]([CH:36]([C:2]3[CH:7]=[CH:6][C:5]([S:8][CH:9]4[CH2:11][CH2:10]4)=[CH:4][CH:3]=3)[OH:37])=[N:24][C:25]=2[O:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH2:18][CH2:19]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 223501051-Bromo-4-cyclopropylthiobenzeneHCID 86658014HCID 86658014, compoundHCID 178418339Butyllithium

Product 1

HCID 67400247{5-Cyclopropyl-6-[(4-methoxybenzyl)oxy]pyridin-2-yl}[4-(cyclopropylsulfanyl)phenyl]methanolYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (4-bromophenyl)(cyclopropyl)sulfane (440 mg) in tetrahydrofuran (10 mL) was cooled to −78° C., and n-butyllithium (2.6 M, 0.74 mL) was slowly added dropwise, followed by stirring for 30 minutes. A solution of 5-cyclopropyl-6-[(4-methoxy benzyl)oxy]pyridine-2-carbaldehyde (417 mg) in tetrahydrofuran (5 mL) was slowly added dropwise, and the mixture was stirred at −78° C. for 4.5 hours. The reaction solution was stirred in an ice bath and a saturated ammonium chloride solution was added, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5→62:38) to give {5-cyclopropyl-6-[(4-methoxybenzyl)oxy]pyridin-2-yl}[4-(cyclopropylsulfanyl)phenyl]methanol as a yellow oil (469 mg, 73%).

Workup

  1. stirringthe mixture was stirred at −78° C. for 4.5 hours
  2. stirringThe reaction solution was stirred in an ice bath
  3. extractionfollowed by extraction with chloroform
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5→62:38)

Sources & evidence

ORD record
ord-2ff5efe37b154b2497bcde72ffa813e7
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Reaction notes

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