Cesium carbonate → (R)-(1-(1-(tert-Butoxycarbonyl)pyrrolidin-3-yl)-1H-pyrazol-4-yl)boronic acid pinacol ester

HRID 911986Notes

Reaction equation

HRID 911986 reaction equation
[CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[C:15]([O:19][C:20]([N:22]1[CH2:26][CH2:25][C@H:24](OS(C)(=O)=O)[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:26][CH2:25][C@@H:24]([N:12]2[CH:13]=[C:9]([B:4]3[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]3)[CH:10]=[N:11]2)[CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 11032777(S)-1-Boc-3-methanesulfonyloxy-pyrrolidine

Product 1

HCID 67402459(R)-(1-(1-(tert-Butoxycarbonyl)pyrrolidin-3-yl)-1H-pyrazol-4-yl)boronic acid pinacol esterYield 33.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.856 g, 4.41 mmol), (S)-3-methanesulfonyloxy-pyrrolidine-1-carboxylic acid tert-butyl ester (1.17 g, 4.41 mmol) and Cs2CO3 (2.16 g, 6.61 mmol) in anhydrous DMF (11.7 mL) was heated to 100° C. for 16 h. The reaction mixture was allowed to cool to rt and was partitioned between EtOAc and H2O and separated. The aqueous was re-extracted with EtOAc (3×) and the combined organic fractions were washed with H2O (3×), brine (2×), dried over Na2SO4, filtered and concentrated in vacuo resulting in a crude brown oil. The reaction mixture was purified by chromatography on silica gel [eluting with 12% EtOAc in CHCl3]resulting in 538 mg, 33% yield of the title compound as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 1.31 (s, 12H), 1.46 (s, 9H), 2.36 (q, J=7.0 Hz, 2H), 3.46-3.78 (m, 3H), 3.80-3.91 (m, 1H), 4.89 (quint, J=6.1 Hz, 1H), 7.73 (s, 1H), 7.80 (s, 1H).

Workup

  1. customwas partitioned between EtOAc and H2O
  2. customseparated
  3. extractionThe aqueous was re-extracted with EtOAc (3×)
  4. washthe combined organic fractions were washed with H2O (3×), brine (2×)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customresulting in a crude brown oil
  9. customThe reaction mixture was purified by chromatography on silica gel [eluting with 12% EtOAc in CHCl3]

Sources & evidence

ORD record
ord-5421926c954a4cb7a5ada16a160684ed
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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