Tetrahydrofuran → HCID 86682359, compound

HRID 2283607Notes

Reaction equation

HRID 2283607 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].O1CCCC1.[F:16][C:17]1[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][C:20]([OH:27])=[C:19]([C:28]2[CH:33]=[CH:32][N:31]=[N:30][CH:29]=2)[CH:18]=1.[C:34]([O:38][C:39](=[O:58])[N:40]([S:46]([C:49]1[CH:54]=[C:53]([Cl:55])[C:52](F)=[CH:51][C:50]=1[F:57])(=[O:48])=[O:47])[C:41]1[N:42]=[CH:43][S:44][CH:45]=1)([CH3:37])([CH3:36])[CH3:35].[Cl-].[NH4+]>CN(C)C=O.O>[C:34]([O:38][C:39](=[O:58])[N:40]([S:46]([C:49]1[CH:54]=[C:53]([Cl:55])[C:52]([O:27][C:20]2[CH:21]=[C:22]([C:23]([F:25])([F:26])[F:24])[C:17]([F:16])=[CH:18][C:19]=2[C:28]2[CH:33]=[CH:32][N:31]=[N:30][CH:29]=2)=[CH:51][C:50]=1[F:57])(=[O:47])=[O:48])[C:41]1[N:42]=[CH:43][S:44][CH:45]=1)([CH3:37])([CH3:35])[CH3:36]

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 59436581Tert-butyl (5-chloro-2,4-difluorophenyl)sulfonyl(thiazol-4-yl)carbamateHCID 136365476HCID 136365476, compound

Product 1

HCID 86682359HCID 86682359, compoundYield 53.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 1.0 M solution of lithium hexamethyldisilazide in tetrahydrofuran (7.55 mL, 7.55 mmol) was added to a solution of 4-fluoro-2-pyridazin-4-yl-5-(trifluoromethyl)phenol (Preparation 11, 1.30 g, 5.04 mmol) in N,N-dimethylformamide (30 mL). After stirring for 5 minutes, tert-butyl-[(5-chloro-2,4-difluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate (Preparation 4, 2.07 g, 5.04 mmol) was added and the reaction mixture stirred at ambient temperature. After 18 hours, the reaction mixture was diluted with water, neutralized with saturated aqueous ammonium chloride, and extracted with ethyl acetate (×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated onto diatomaceous earth. The residue was purified by automated silica gel flash chromatography (hexanes to ethyl acetate gradient elution) to afford tert-butyl({5-chloro-2-fluoro-4-[4-fluoro-2-pyridazin-4-yl-5-(trifluoromethyl)phenoxy]phenyl}sulfonyl)1,3-thiazol-4-ylcarbamate (1.75 g).

Workup

  1. stirringthe reaction mixture stirred at ambient temperature
  2. waitAfter 18 hours
  3. extractionextracted with ethyl acetate (×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated onto diatomaceous earth
  8. customThe residue was purified by automated silica gel flash chromatography (hexanes to ethyl acetate gradient elution)

Sources & evidence

ORD record
ord-019bdf05dfba4294933f28f5f44381b9
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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