Bromoacetic Acid → 2-(1-(4-Chloro-3-fluorophenyl)cyclobutoxy)acetic acid

HRID 885131Notes

Reaction equation

HRID 885131 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([OH:14])[CH2:13][CH2:12][CH2:11]2)=[CH:6][C:5]=1[F:15].Br[CH2:17][C:18]([OH:20])=[O:19]>CN(C)C=O>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([O:14][CH2:17][C:18]([OH:20])=[O:19])[CH2:11][CH2:12][CH2:13]2)=[CH:6][C:5]=1[F:15]

Participants

5

Reactant 3

HCID 6227Bromoacetic AcidHCID 24758Sodium hydrideHCID 68719259HCID 68719259, compound

Product 1

HCID 687209032-(1-(4-Chloro-3-fluorophenyl)cyclobutoxy)acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To an ambient suspension of NaH (0.341 g, 8.52 mmol, 60% dispersion in mineral oil) in N,N-dimethylformamide (7 mL) was added a solution of Example 56A (0.342 g, 1.71 mmol) in N,N-dimethylformamide (1 mL) dropwise. The reaction was stirred for 0.5 h, and 2-bromoacetic acid (0.474 g, 3.41 mmol) was added as a solution in N,N-dimethylformamide (2 mL) dropwise. The reaction was stirred at room temperature for 24 h and was then quenched by the slow addition of H2O (10 mL) and diethyl ether (15 mL). The layers were separated, and the organic discarded. The aqueous was acidified to pH ˜4-5 with 10% HCl and was extracted with diethyl ether (3×15 mL). The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a yellow oil, which was used without further purification in the subsequent step, MS (ESI) m/z 259[M+H]+.

Workup

  1. stirringThe reaction was stirred at room temperature for 24 h
  2. customwas then quenched by the slow addition of H2O (10 mL) and diethyl ether (15 mL)
  3. customThe layers were separated
  4. extractionwas extracted with diethyl ether (3×15 mL)
  5. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give a yellow oil, which
  9. customwas used without further purification in the subsequent step, MS (ESI) m/z 259[M+H]+

Sources & evidence

ORD record
ord-589a6028fd844ec897740807178e2f44
Source dataset
uspto-grants-2012_08
Patent number
US08242139B2

Reaction notes

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