HCID 67508601, compound → HCID 67517470, compound

HRID 2038793Notes

Reaction equation

HRID 2038793 reaction equation
CO[C:3](=[O:27])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([C:16]3([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:17]3)=[CH:14][CH:15]=2)=[CH:6][CH:5]=1.[CH3:28][CH2:29][Mg+].[Br-]>C1COCC1>[C:23]([O:22][C:20](=[O:21])[NH:19][C:16]1([C:13]2[CH:14]=[CH:15][C:10]([C:7]3[CH:8]=[CH:9][C:4]([C:3]4([OH:27])[CH2:29][CH2:28]4)=[CH:5][CH:6]=3)=[CH:11][N:12]=2)[CH2:17][CH2:18]1)([CH3:25])([CH3:26])[CH3:24]

Participants

4

Reactant 2

HCID 67508601HCID 67508601, compoundHCID 178461630HCID 178461630, compound2×

Product 1

HCID 67517470HCID 67517470, compoundYield 77.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-[6-(1-tert-butoxycarbonylamino-cyclopropyl)-pyridin-3-yl]-benzoic acid methyl ester (0.68 g, 1.8 mmol) in THF (20 mL) was added Ti(Oi-Pr)4 (0.54 mL, 1.8 mmol). To this mixture was slowly added EtMgBr (3M in Et2O, 1.2 mL, 3.7 mmol) over 30 minutes. The reaction was allowed to stir at room temperature for 1 h. Ti(Oi-Pr)4 (1.1 mL, 3.2 mmol) and EtMgBr (3M in Et2O, 1.2 mL, 3.7 mmol) were again added to the solution and the reaction stirred for 30 minutes. The mixture was quenched with water and extracted with EtOAc (3×100 mL). The combined extracts were washed with water, brine and dried with MgSO4. The mixture was filtered, concentrated and the residue purified by reverse phase HPLC to give (1-{5-[4-(1-hydroxy-cyclopropyl)-phenyl]-pyridin-2-yl}-cyclopropyl)-carbamic acid tert-butyl ester (0.05 g, 1.4 mmol) as a brown solid, m/z 367.7 [M+H]+.

Workup

  1. customover 30 minutes
  2. stirringthe reaction stirred for 30 minutes
  3. customThe mixture was quenched with water
  4. extractionextracted with EtOAc (3×100 mL)
  5. washThe combined extracts were washed with water, brine
  6. dry with materialdried with MgSO4
  7. filtrationThe mixture was filtered
  8. concentrationconcentrated
  9. customthe residue purified by reverse phase HPLC

Sources & evidence

ORD record
ord-e999ec2742c04ae5809c0908fec52848
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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