Triethylamine → HCID 86689559, compound

HRID 1853894Notes

Reaction equation

HRID 1853894 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[C:4]([F:12])[CH:3]=1.C(N(CC)CC)C.CC(C)(C)C(Cl)=O.[CH2:27]1[O:32][C:30](=[O:31])[NH:29][C@H:28]1[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1(C)C=CC=CC=1.O1CCCC1.S(=O)(=O)(O)[O-].[Na+]>[CH2:33]([C@H:28]1[CH2:27][O:32][C:30](=[O:31])[N:29]1[C:9](=[O:11])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[F:12])[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 2733832Lithium HexamethyldisilazideHCID 140537922-(4-Bromo-2-fluorophenyl)acetic acid

Product 1

HCID 86689559HCID 86689559, compoundYield 42%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 516919Sodium BisulfateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (2-(4-bromo-2-fluorophenyl)acetic acid) (3 g, 13 mmol) and triethylamine (2.5 mL, 14 mmol) in toluene (50 mL) at 0° C. was added trimethylacetyl chloride (6.1 mL, 65 mmol) dropwise. After 10 mins the reaction mixture was cooled to −78° C. In a separate flask, to a solution of (S-(+)-4-benzyl-2-oxazolidinone (2.5 g, 14 mmol) in tetrahydrofuran (50 mL) at −78° C. was added LiHMDS (1 M in hexane, 17 mL, 17 mmol)) until yellowish color persisted. After 10 mins the resulting solution was transferred through a cannula into the suspension of mixed anhydride prepared as described above. The reaction mixture was allowed to reach rt over the period of 4 h, then diluted with saturated aqueous sodium bisulfate (ca. 20 mL), and extracted with ethyl acetate (ca. 100 mL). The extract was washed with brine (2×50 mL), dried over sodium sulfate, and evaporated under vacuum. Flash chromatography of the residue followed by trituration (hexanes) afforded the desired product (2.1 g, 42%) as white solid. ESI MS m/z 393 [C18H15BrFNO3+H]+

Workup

  1. customprepared
  2. customto reach rt over the period of 4 h
  3. extractionextracted with ethyl acetate (ca. 100 mL)
  4. washThe extract was washed with brine (2×50 mL)
  5. dry with materialdried over sodium sulfate
  6. customevaporated under vacuum

Sources & evidence

ORD record
ord-78b84d1fb7d643c4b77569e6751608e3
Source dataset
uspto-grants-2015_02
Patent number
US08962648B2

Reaction notes

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