Water → 3-chloro-2,4-difluoro-N-(2-hydroxyethyl)-N-methylbenzamide

HRID 548665Notes

Reaction equation

[Si]([O:8][CH2:9][CH2:10][N:11]([CH3:23])[C:12](=[O:22])[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Cl:20])[C:14]=1[F:21])(C(C)(C)C)(C)C.OC1C=C(C=C(O[C@@H](C)CO[Si](C(C)C)(C(C)C)C(C)C)C=1)C(NC1C=CN(C)N=1)=O.C(=O)([O-])[O-].[K+].[K+].O>CC(N(C)C)=O>[Cl:20][C:15]1[C:14]([F:21])=[C:13]([CH:18]=[CH:17][C:16]=1[F:19])[C:12]([N:11]([CH2:10][CH2:9][OH:8])[CH3:23])=[O:22]

Participants

Conditions

Temperature: 160 °C

Procedure

N-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamide (100 mg, 0.275 mmol) was added to 3-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzamide (123 mg, 0.275 mmol) and potassium carbonate (76 mg, 0.551 mmol) in dry dimethylacetamide. The mixture was heated in a Smith Creator microwave at 160° C. for 2 hours. Water (25 mL) was added to the reaction mixture and extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried (MgSO4), filtered and evaporated. Purification by column chromatography on silica, eluting with 50-100% ethyl acetate in hexanes, gave the title compound as a pale yellow oil (500 mg). 1H NMR δ (CDCl3): 1.29 (d, 3H), 2.09 (t, 1H), 3.23 (s, 3H), 3.59 (t, 2H), 3.71-3.76 (m, 2H), 3.79 (s, 3H), 4.54 (t, 2H), 4.50-4.57 (m, 1H), 6.74 (t, 1H), 6.77 (d, 1H), 6.80 (d, 1H), 7.04 (t, 1H), 7.23 (t, 1H), 7.28 (d, 1H), 7.70 (d, 1H), 8.52 (s, 1H)

Workup

extractionextracted with ethyl acetate (3×30 mL)
dry with materialThe combined organic extracts were dried (MgSO4)
filtrationfiltered
customevaporated
customPurification by column chromatography on silica
washeluting with 50-100% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-7ba8f8461af649e48ab97838a29cf2ac
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07943607B2

Reaction notes

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