Sodium hydride → tert-Butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate

HRID 216721Notes

Reaction equation

HRID 216721 reaction equation
[H-].[Na+].[CH3:3][C:4]1([CH3:16])[C:8]([CH3:10])([CH3:9])[O:7][B:6]([C:11]2[CH:12]=[N:13][NH:14][CH:15]=2)[O:5]1.[C:17]([O:21][C:22]([N:24]1[CH2:27][CH:26](OS(C)(=O)=O)[CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]>CN(C=O)C>[C:17]([O:21][C:22]([N:24]1[CH2:27][CH:26]([N:14]2[CH:15]=[C:11]([B:6]3[O:7][C:8]([CH3:9])([CH3:10])[C:4]([CH3:16])([CH3:3])[O:5]3)[CH:12]=[N:13]2)[CH2:25]1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 10753243Tert-butyl 3-(methanesulfonyloxy)azetidine-1-carboxylate

Product 1

HCID 54576812tert-Butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

NaH (60% in mineral oil, 222 mg, 5.6 mmol) is added portionwise to a stirred solution of 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (1.10 g, 5.56 mmol) in DMF (20 ml). The resulting mixture is stirred for 1 h at 0° C. and then allowed to warn to RT. A solution of 3-Methanesulfonyloxy-azetidine-1-carboxylic acid tert-butyl ester (as obtained in preparation 80, 1.39 g, 5.56 mmol) in DMF (3 ml) is then added dropwise. After complete addition, the reaction mixture is heated at 95° C. for 5 h. The reaction is quenched with water and extracted with EtOAc several times. The combined organic layers are washed with brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography on a 40 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2: TBDME from 1:0=>0:1) to afford the title compound as a colorless foam, Rt=1.200 min (Acquity HPLC BEH C18, 2.1×50 mm, 1.7 micron, detection 215 nM, 0.1 min 2% CH3CN in H2O, 2% to 100% CH3CN in H2O in 1.5 min, 0.4 min 100% CH3CN+0.1% TFA, flow rate 1.0 ml/min); MS: 350 (M+1)+.

Workup

  1. customto warn to RT
  2. additionAfter complete addition
  3. temperaturethe reaction mixture is heated at 95° C. for 5 h
  4. customThe reaction is quenched with water
  5. extractionextracted with EtOAc several times
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate is concentrated in vacuo
  10. customThe residue is purified by chromatography on a 40 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2: TBDME from 1:0=>0:1)

Sources & evidence

ORD record
ord-e311f1e61f8b4f3db03b64f3f73a7d09
Source dataset
uspto-grants-2012_06
Patent number
US08193189B2

Reaction notes

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