Triethylamine → HCID 67404578, compound

HRID 1876439Notes

Reaction equation

HRID 1876439 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([F:15])=[CH:13][C:12]([CH2:16][CH:17]([CH3:21])[C:18]([OH:20])=[O:19])=[CH:11][C:10]=1[F:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[CH2:37]([C@@H:44]1[CH2:48][O:47][C:46](=[O:49])[NH:45]1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C([Li])CCC>O1CCCC1>[CH2:37]([C@@H:44]1[CH2:48][O:47][C:46](=[O:49])[N:45]1[C:18](=[O:20])[C@@H:17]([CH3:21])[CH2:16][C:12]1[CH:11]=[C:10]([F:22])[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:14]([F:15])[CH:13]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1.[CH2:37]([C@@H:44]1[CH2:48][O:47][C:46](=[O:49])[N:45]1[C:18](=[O:19])[C@H:17]([CH3:21])[CH2:16][C:12]1[CH:13]=[C:14]([F:15])[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:10]([F:22])[CH:11]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 2734969(R)-4-Benzyl-2-oxazolidinone2×HCID 59455495HCID 59455495, compound2×HCID 178418339Butyllithium

Product 2

HCID 67404578HCID 67404578, compoundHCID 67408180HCID 67408180, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(4-(benzyloxy)-3,5-difluorophenyl)-2-methylpropanoic acid (753) (0.99 g, 3.23 mmol) in tetrahydrofuran (2.5 mL) at 0° C. was added triethylamine (0.50 mL, 3.57 mmol) and pivaloyl chloride (0.44 mL, 3.57 mmol) and the reaction was stirred for 30 minutes. In a separate flask (R)-4-benzyloxazolidin-2-one (0.48 g, 2.69 mmol) was dissolved in tetrahydrofuran (4 mL) and cooled to −78° C. n-butyllithium (1.77 mL, 2.69 mmol, 1.52 M in hexanes) was added and the reaction was stirred for 30 minutes. The solution of 3-(4-(benzyloxy)-3,5-difluorophenyl)-2-methylpropanoic acid was added to the (R)-4-benzyloxazolidin-2-one solution and stirred at −78° C. for 3 hours and at room temperature for 30 minutes. The reaction was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with hexanes and EtOAc to afford the two diastereomers (R)-4-benzyl-3-((S)-3-(4-(benzyloxy)-3,5-difluorophenyl)-2-methylpropanoyl)oxazolidin-2-one and (R)-4-benzyl-3-((R)-3-(4-(benzyloxy)-3,5-difluorophenyl)-2-methylpropanoyl)oxazolidin-2-one. The benzyl group was removed with Pd/C under a hydrogen atmosphere as previously described for the synthesis of compound (9) to provide (R)-4-benzyl-3-((S)-3-(3,5-difluoro-4-hydroxyphenyl)-2-methylpropanoyl)oxazolidin-2-one (754) and (R)-4-benzyl-3-((R)-3-(3,5-difluoro-4-hydroxyphenyl)-2-methylpropanoyl)oxazolidin-2-one (755).

Workup

  1. additionwas added
  2. stirringthe reaction was stirred for 30 minutes
  3. stirringstirred at −78° C. for 3 hours and at room temperature for 30 minutes
  4. customThe reaction was quenched with saturated ammonium chloride
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography on silica gel with hexanes and EtOAc

Sources & evidence

ORD record
ord-9ade4c9c5a7641bd95e8ed77517ebbb1
Source dataset
uspto-grants-2012_11
Patent number
US08309600B2

Reaction notes

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