Sodium Hydroxide → {1-[5-(1H-pyrazol-4-yl)-pyridin-2-yl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 2038758Notes

Reaction equation

HRID 2038758 reaction equation
[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15](I)=[CH:14][N:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(OC([N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1)=O)(C)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>COCCOC.O.CCO>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:30]3[CH:31]=[N:27][NH:28][CH:29]=3)=[CH:14][N:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 67509277Tert-butyl (1-(5-iodopyridin-2-YL)cyclobutyl)carbamate

Product 1

HCID 68379199{1-[5-(1H-pyrazol-4-yl)-pyridin-2-yl]-cyclobutyl}-carbamic acid tert-butyl esterYield 103.4%

Reagents, catalysts & solvents 1

HCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of [1-(5-iodo-pyridin-2-yl)-cyclobutyl]-carbamic acid tert-butyl ester (0.46 g, 1.23 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (0.4 g, 1.35 mmol), and PdCl2(dppf)Cl2.dichloromethane complex (0.2 g, 0.25 mmol) in DME/H2O/EtOH (4 mL, 7:3:2) in a sealable microwave tube was added 1M K3PO4 (1.5 mL, 1.5 mmol). The tube was sealed and heated in microwave at 100° C. for 10 minutes and then 120° C. for 20 minutes. 2M NaOH was added (2 mL) and stirred for 10 minutes. The solution was extracted with EtOAc (100 mL). The organic phase was washed with brine, dried over MgSO4, filtered through diatomaceous earth, and concentrated. The crude oil was purified via normal phase flash chromatography on silica gel eluting with 0-6% MeOH/CH2Cl2, to afford {1-[5-(1H-pyrazol-4-yl)-pyridin-2-yl]-cyclobutyl}-carbamic acid tert-butyl ester (0.40 g) as a brown solid, m/z 315.5 [M+H]+.

Workup

  1. customThe tube was sealed
  2. extractionThe solution was extracted with EtOAc (100 mL)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered through diatomaceous earth
  6. concentrationconcentrated
  7. customThe crude oil was purified via normal phase flash chromatography on silica gel eluting with 0-6% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-aa4f67022714402f8362e0d108ff037c
Source dataset
uspto-grants-2013_11
Patent number
US08575360B2

Reaction notes

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