l-(2,4-Difluoro-phenoxy)-cyclopropanecarboxylic acid
Preparation of l-(2,4-Difluoro-phenoxy)-cyclopropanecarboxylic acid used in Example Ll is described below:
(L1-I) (L-I-Ii) (LI-IIl) 4-Bromo-2-(2,4-difluoro-phenoxy)-butyric acid methyl ester (Ll-I):
To a solution of 2,4-difluro phenol ( 0.35 g, 2.73 mmol) in DMF (5 ml), added potassium carbonate ( 0.38 g, 2.73 mmol) and 2,4-Dibromo-butyric acid methyl ester (0.71 g, 2.74 mmol) and heated at 60 0C for 3 h. Reaction mixture was cooled to r.t. It was then extracted in EtO Ac( 30 ml) and washed with brine( 2X10 ml), dried over Na2SO4 and concentrated under reduced pressure to obtain crude product, purification on silica gel to yield 4-Bromo-2-(2,4-difluoro-phenoxy)-butyric acid methyl ester (0.52 g, 61 %). 1H NMR (400 MHz, CDCl3): δ 12.42-2.56 (m, 2H), 3.53-3.71 (m, 2H), 3.77 (s, 3H), 4.81 (dd, J=3.6 and 8.8 Hz, IH), 6.72-6.80 (m,lH), 6.85-6.90 (m, IH), 6.95-7.02 (m, IH).
l-(2,4-Difluoro-phenoxy)-cyclopropanecarboxylic acid methyl ester (Ll-II):
A solution of 4-Bromo-2-(2,4-difluoro-phenoxy)-butyric acid methyl ester (3.167 g,
10.29 mmol) in THF ( 40 ml) was added to a suspension of potassium tert butoxide ( 1.148 g, 10.26 mmol) in THF (20 ml) and the reaction mixture was heated at 6O0C for 4 hr. Reaction mixture was cooled to room temp, quenched with brine (5ml) extracted in ether (50 ml) and washed with brine (2X5ml), dried over Na2SO4 and concentrated under reduced pressure to obtain crude product, l-(2,4-Difluoro-phenoxy)-cyclopropanecarboxylic acid methyl ester (1.9 g, 81 %) which was used as such in the next step. l-(2,4-Difluoro-phenoxy)-cyclopropanecarboxylic acid (Ll-III):
To a solution of l-(2,4-Difluoro-phenoxy)-cyclopropanecarboxylic acid methyl ester ( 1.89 g, 8.28 mmol) in THF (20 ml) added a solution of LiOH( 0.86 g, 20.7 mmol) in water (5ml) was added, and mixture is stirred at r.t. for 18 h. Solvent was evaporated at reduced pressure acidified with IN HCl (pH~ 2) and extracted in ethyl acetate (70 ml) and washed with brine (2XlOmI), dried over Na2SO4 and concentrated under reduced pressure to obtain l-(2,4-Difluoro-phenoxy)-cyclopropanecarboxylic acid ( 1.16 g, 66%). 1H NMR (400 MHz, CDCl3): δ 1.46 (dd, J=5.6 and 9.2 Hz, IH), 1.71 (dd, J=5.6 and 9.2 Hz, IH), 2.27-2.31 (m, IH), 3.97-4.0 (m, IH), 4.85 (t, J=5.6 Hz, IH), 6.77-83 (m, IH), 6.85-6.92 (m, IH), 7.0-7.06 (m, IH).
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Lund khwar. pakistan
Lund
Khwar, also Lundkhwar | Urdu: لوندخوڑ) and pronounced "/Lu:/+/nd/,
/Kh/+/va'/+/r:/" is a historical village and union council of Takht Bhai
Tehsil in Mardan District of Khyber-Pakhtunkhwa, Pakistan. It is
located at 34°23'22 N 71°58'51 E, with an altitude of 371 metres
(1220 feet). The name "Lund Khwar"
literally means "the ever-flowing stream or brook". Origins of the
founding of Lund Khwar are shrouded in mystery. Archaeological and
historical evidence clue towards the Gandharan era. Earliest written
accounts of the village trace it back to the 8th century, with the
arrival of the Uthman Khel branch of the Yousafzai, and in the 15th
century, by the Khattak tribesmen of the Afghans. Currently it is a
major town near the entrance to the Malakand mountains. Alternatively,
there is also a Lund Khwar in the Paktika Province of Afghanistan.
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