Sulfuric acid magnesium salt (1:1) → (6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridyl)methanol

HRID 226301Notes

Reaction equation

HRID 226301 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[CH2:11]([N:18]1[CH2:22][CH2:21][C@@H:20]([NH:23][C:24]2[C:34]([Cl:35])=[CH:33][C:27]([C:28](OCC)=[O:29])=[CH:26][N:25]=2)[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[Na+].[O-]S([O-])(=O)=O.[Mg+2]>C1(C)C=CC=CC=1.CO>[CH2:11]([N:18]1[CH2:22][CH2:21][C@@H:20]([NH:23][C:24]2[N:25]=[CH:26][C:27]([CH2:28][OH:29])=[CH:33][C:34]=2[Cl:35])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 9855836Potassium sodium tartarateHCID 21225700DiisobutylaluminumhydrideHCID 68967686ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinate

Product 1

HCID 68962858(6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridyl)methanolYield 45%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent2×

Procedure

A diisobutylaluminum hydride in toluene solution (15.7 ml) was dropwise added to a solution of ethyl 6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloronicotinate (4.7 g) in toluene (50 ml) with stirring at −30˜−50° C. under atmospheric pressure of nitrogen, and the reaction mixture was stirred at −20˜−40° C. for 2 hours. A MeOH (5 ml) was added to a reaction mixture at −40° C. and saturated sodium potassium tartrate aqueous solution (10 ml) and MgSO4 (10 g) and the resultant mixture was stirred at ambient temperature for 20 minutes. The reaction mixture was filtrated and the filtrate was dried over MgSO4. The solvent was evaporated in vacuo and the residue was chromatographed on silicagel eluting with AcOEt-MeOH (9:1). The eluted fractions containing the desired product were collected and evaporated in vacuo to give (6-{[(3R)-1-benzyl-3-pyrrolidinyl]amino}-5-chloro-3-pyridyl)methanol (1.87 g).

Workup

  1. stirringthe reaction mixture was stirred at −20˜−40° C. for 2 hours
  2. filtrationThe reaction mixture was filtrated
  3. dry with materialthe filtrate was dried over MgSO4
  4. customThe solvent was evaporated in vacuo
  5. customthe residue was chromatographed on silicagel
  6. washeluting with AcOEt-MeOH (9:1)
  7. additionThe eluted fractions containing the desired product
  8. customwere collected
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-ab7104a7bb75428aac2771305ab8bbe2
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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