3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenol → 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-(3-hydroxyphenyl)-5-methylpyridin-2-yl)cyclopropanecarboxamide

HRID 2188956Notes

Reaction equation

HRID 2188956 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=2)O1.Cl[C:18]1[N:23]=[C:22]([NH:24][C:25]([C:27]2([C:30]3[CH:40]=[CH:39][C:33]4[O:34][C:35]([F:38])([F:37])[O:36][C:32]=4[CH:31]=3)[CH2:29][CH2:28]2)=[O:26])[CH:21]=[CH:20][C:19]=1[CH3:41]>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:38][C:35]1([F:37])[O:34][C:33]2[CH:39]=[CH:40][C:30]([C:27]3([C:25]([NH:24][C:22]4[CH:21]=[CH:20][C:19]([CH3:41])=[C:18]([C:9]5[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=5)[N:23]=4)=[O:26])[CH2:29][CH2:28]3)=[CH:31][C:32]=2[O:36]1

Participants

6

Reactant 2

HCID 27346233-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 59165796N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamide

Product 1

HCID 591658801-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-(3-hydroxyphenyl)-5-methylpyridin-2-yl)cyclopropanecarboxamideYield 78.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (132 mg, 0.600 mmol) and N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (183 mg, 0.500 mmol) in DME (3 mL) and 2 M Na2CO3 (0.5 mL) was added Pd(PPh3)4 (29 mg, 0.025 mmol). The mixture was heated in microwave oven at 120° C. for 30 min. The mixture was partitioned between ethyl acetate and H2O, and the aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography to afford 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(6-(3-hydroxyphenyl)-5-methylpyridin-2-yl)cyclopropanecarboxamide (166 mg, 78%). 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J=8.4 Hz, 1H), 7.88 (s, 1H), 7.62 (d, J=8.5 Hz, 1H), 7.24 (t, J=7.9 Hz, 1H), 7.18-7.15 (m, 2H), 6.91-6.88 (m, 2H), 6.79-6.78 (m, 1H), 6.73-6.69 (m, 2H), 2.29 (s, 3H), 1.75 (q, J=3.6 Hz, 2H), 1.15 (q, J=3.6 Hz, 2H). MS (ESI) m/e (M+H+) 426.2.

Workup

  1. customThe mixture was partitioned between ethyl acetate and H2O
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-c473dbc0a03748cea0d25d575f02fd2b
Source dataset
uspto-grants-2012_12
Patent number
US08324207B2

Reaction notes

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