Water → 3-[5-Allyl-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamide

HRID 538512Notes

Reaction equation

HRID 538512 reaction equation
Br[C:2]1[S:6][C:5]([CH2:7][O:8][C:9]2[C:10]([F:19])=[C:11]([C:15]([F:18])=[CH:16][CH:17]=2)[C:12]([NH2:14])=[O:13])=[N:4][C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1.[CH2:28]([Sn](CCCC)(CCCC)CCCC)[CH:29]=[CH2:30].O>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:30]([C:2]1[S:6][C:5]([CH2:7][O:8][C:9]2[C:10]([F:19])=[C:11]([C:15]([F:18])=[CH:16][CH:17]=2)[C:12]([NH2:14])=[O:13])=[N:4][C:3]=1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)[CH:29]=[CH2:28]

Participants

6

Reactant 3

HCID 962WaterHCID 90628AllyltributylstannaneHCID 594026583-[5-Bromo-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamide

Product 1

HCID 594026523-[5-Allyl-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamideYield 144.1%

Reagents, catalysts & solvents 2

HCID 57646695Palladium;tetraphenyl-lambda5-phosphaneCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-[5-bromo-4-(4-methoxy-phenyl)-thiazol-2-ylmethoxy]-2,6-difluoro-benzamide (0.1 g, 0.0002 mol) in 5 ml of anhydrous DMF was added Allyl tributyltin (0.072 g, 0.0002 mol) and degassed the reaction mixture for the 10 minutes. Then added tetraphenylphosphine Palladium (0) (0.025 g, 0.00002 mol). The reaction mixture was heated at 120° C. for 12 h under the nitrogen atmosphere. Then reaction mixture was cooled to rt. 100 ml of water was added into it and extracted the compound with ethyl acetate, The combined organic layers were dried over anhydrous Na2SO4, and evaporated to dryness under reduced pressure. The compound was purified by column chromatography on silica (230-400μ) using methanol/DCM (2:98) as the eluent to provide the title compound as brown solid (0.120 g, 60%). 1H NMR (DMSO-d6, 400 MHz): δ 3.79 (s, 3H), 5.11-5.14 (m, 1H), 5.16 (s, 1H), 5.48 (s, 2H), 5.57 (s, 1H), 5.99-6.06 (m, 1H), 7.03 (d, 2H, J=8.4 Hz (o-coupling), 7.11 (dt, 1H, J=9.2 Hz (o-coupling), 7.36-7.42 (m, 1H), 7.56 (d, 2H, J=8.8 Hz (o-coupling), 7.88 (broad s, 1H), 8.16 (broad s, 1H). MS ES+ (417.06), HPLC (method 5) Rt=16.96 min.

Workup

  1. customdegassed the reaction mixture for the 10 minutes
  2. customThen reaction mixture
  3. temperaturewas cooled to rt
  4. extractionextracted the compound with ethyl acetate
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. customevaporated to dryness under reduced pressure
  7. customThe compound was purified by column chromatography on silica (230-400μ)

Sources & evidence

ORD record
ord-57f624990ddb43369d54b14219f7f569
Source dataset
uspto-grants-2014_10
Patent number
US08865736B2

Reaction notes

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