Sodium Bicarbonate → (2S)-2-{3-[5-(4,5-Dihydro-1,3-thiazol-2-yl)-1H-pyrrol-2-yl]-5-[4-(methylsulfonyl)phenoxy]phenoxy}propan-1-ol

HRID 1964543Notes

Reaction equation

HRID 1964543 reaction equation
C[O:2][CH2:3][C@H:4]([CH3:33])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28]3[S:29][CH2:30][CH2:31][N:32]=3)=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)[CH:11]=1.ClCCl.B(Br)(Br)Br.C(=O)([O-])O.[Na+]>ClCCl>[S:29]1[CH2:30][CH2:31][N:32]=[C:28]1[C:26]1[NH:27][C:23]([C:8]2[CH:7]=[C:6]([CH:11]=[C:10]([O:12][C:13]3[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)[CH:9]=2)[O:5][C@@H:4]([CH3:33])[CH2:3][OH:2])=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 22277759Boron tribromide dichloromethaneHCID 580654612-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrol-2-yl)-4,5-dihydro-1,3-thiazole

Product 1

HCID 58065522(2S)-2-{3-[5-(4,5-Dihydro-1,3-thiazol-2-yl)-1H-pyrrol-2-yl]-5-[4-(methylsulfonyl)phenoxy]phenoxy}propan-1-olYield 54.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

2-(5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-1H-pyrrol-2-yl)-4,5-dihydro-1,3-thiazole (88 mg, 0.18 mmol) synthesized in Example (25c) was dissolved in dichloromethane (5 mL), and cooled to −78° C., a 1.0 mol/L boron tribromide dichloromethane solution (0.22 mL, 0.22 mmol) was added under nitrogen atmosphere. After the temperature was raised naturally and the solution was stirred at room temperature for 1 hour, subsequently a saturated aqueous sodium hydrogencarbonate solution was added to neutralize the reaction solution, followed by extraction with dichloromethane (60 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=40%-100%) to afford the desired product (46 mg, yield 54%) as a pale yellow solid.

Workup

  1. temperatureAfter the temperature was raised naturally
  2. extractionfollowed by extraction with dichloromethane (60 mL)
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=40%-100%)

Sources & evidence

ORD record
ord-f81c266557814845b946404bdca95916
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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