Ethanol → HCID 67508601, compound

HRID 2038792Notes

Reaction equation

HRID 2038792 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1([C:11]2[CH:16]=[CH:15][C:14](I)=[CH:13][N:12]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CO[C:21]1[CH:26]=[CH:25][CH:24](B(O)O)[C:23](=[C:30]=[O:31])[CH:22]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C[CH2:41][OH:42]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:41][O:42][C:30](=[O:31])[C:23]1[CH:22]=[CH:21][C:26]([C:14]2[CH:13]=[N:12][C:11]([C:8]3([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:18])[CH2:10][CH2:9]3)=[CH:16][CH:15]=2)=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 62657Potassium Phosphate, TribasicHCID 58431130[1-(5-Iodo-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl esterHCID 86671821HCID 86671821, compound

Product 1

HCID 67508601HCID 67508601, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of [1-(5-iodo-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester (1.5 g, 4.2 mmol) in DME (4 mL) was added PdCl2(dppf).dichloromethane complex (0.34 g, 0.42 mmol). The solution was transferred to a microwave vial containing (4-methoxy-carbonylphenyl)-boronic acid (0.90 g, 5.0 mmol). K3PO4 (1.1 g, 5.4 mmol) was then added followed by water (1 mL) and EtOH (1 mL). The reaction was heated in a microwave at 100° C. for 10 min. The mixture was diluted with water and extracted with EtOAc (3×50 mL). The combined extracts were washed with water, brine and dried with MgSO4. The mixture was filtered, concentrated and the residue purified by silica gel chromatography (0-100% EtOAc in hexanes) to give 4-[6-(1-tert-butoxycarbonylamino-cyclopropyl)-pyridin-3-yl]-benzoic acid methyl ester (0.75 g, 2.0 mmol) as a yellow solid, m/z 369.7 [M+H]+.

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. washThe combined extracts were washed with water, brine
  3. dry with materialdried with MgSO4
  4. filtrationThe mixture was filtered
  5. concentrationconcentrated
  6. customthe residue purified by silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-473497c70a1f4ba5ae073faface12de9
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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