Ammonium Chloride → 3-(3,5-Dichloro-pyridin-4-ylmethylene)-6-methoxy-1-thiazol-2-yl-1,3-dihydro-isobenzofuran-1-ol

HRID 2297506Notes

Reaction equation

Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C([Li])CCC.[Cl:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([Cl:32])[C:18]=1[CH:19]=[C:20]1[C:28]2[C:23](=[CH:24][C:25]([O:29][CH3:30])=[CH:26][CH:27]=2)[C:22](=[O:31])[O:21]1.[NH4+].[Cl-]>C(OCC)C.C1COCC1.O>[Cl:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([Cl:32])[C:18]=1[CH:19]=[C:20]1[C:28]2[C:23](=[CH:24][C:25]([O:29][CH3:30])=[CH:26][CH:27]=2)[C:22]([C:2]2[S:3][CH:4]=[CH:5][N:6]=2)([OH:31])[O:21]1

Participants

Conditions

Temperature: -80 °C

Procedure

A milky solution of 2-bromothiazole (5.6 g, 34.2 mmoles) in dry ethyl ether (17 ml) was added dropwise to a solution of n-butyl lithium (14.4 ml, 36 mmoles) in dry ethyl ether (50 ml), under N2 at −80° C. The reaction mixture was stirred at −80° C. for 15 minutes, then a solution of 3-(3,5-dichloro-pyridin-4-ylmethylene)-6-methoxy-3H-isobenzofuran-1-one (10 g, 31 mmoles), prepared as described in example 37, in dry THF (60 ml) was slowly added. After 45 minutes at −78° C., the resultant solution was treated with saturated NH4Cl, with water and brought to room temperature. The aqueous phase was separated and extracted with ethyl acetate, decoloured with charcoal, filtered over celite and concentrated under vacuum. The resultant foam was flash cromatographed (eluent petrolatum:ethyl acetate 6:4) obtaining 4.64 g of the title compound (yield: 38%).

Workup

additionwas slowly added
waitAfter 45 minutes at −78° C.
custombrought to room temperature
customThe aqueous phase was separated
extractionextracted with ethyl acetate
filtrationfiltered over celite
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-7067c72834d84f14bf33c5bdef952764
Source dataset: uspto-grants-2002_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06492360B1

Reaction notes

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