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Triethylamine → (4R,5S)-4-Methyl-3-((R)-4-methyl-nonanoyl)-5-phenyl-oxazolidin-2-one

HRID 1167927
Notes
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Reaction equation

HRID 1167927 reaction equation
[CH3:1][C@H:2]([CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:3][CH2:4][C:5]([OH:7])=O.C(N(CC)CC)C.CC(C)(C)C(Cl)=O.[Li+].[Cl-].[CH3:29][C@@H:30]1[CH:34]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:33][C:32](=[O:41])[NH:31]1>C1COCC1>[CH3:29][C@@H:30]1[C@H:34]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:33][C:32](=[O:41])[N:31]1[C:5](=[O:7])[CH2:4][CH2:3][C@H:2]([CH3:1])[CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 433294Lithium ChlorideHCID 6997340(4R)-4-methylnonanoic acidHCID 54201120(4R)-4-methyl-5-phenyl-1,3-oxazolidin-2-one

Product 1

HCID 57037638(4R,5S)-4-Methyl-3-((R)-4-methyl-nonanoyl)-5-phenyl-oxazolidin-2-one
Yield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Compound 154 (6.504 g, 37.76 mmol) was dissolved in THF (95 mL) and cooled to 0° C. Triethylamine (19.74 mL, 141.6 mmol) was added dropwise, followed by dropwise addition of trimethylacetyl chloride (6.98 mL, 56.64 mmol). The thick white suspension was stirred at 0° C. for 90 minutes. LiCl (1.86 g, 41.54 mmol), (4R)-4-methyl-5-phenyl-1,3-oxazolidin-2-one (6.824 g, 38.51 mmol), and THF (70 mL) were added, and the reaction warmed to room temperature overnight. The solvent was evaporated. The solids were taken up in EtOAc, filtered off, and washed generously with EtOAc. The filtrate was washed with water (2×50 mL), and brine. The organics were dried over MgSO4, filtered, and rotovapped. The crude material was chromatographed on silica eluting with 10% EtOAc/hexanes to give 155 as an oil (10.974 g, 88%). 1H NMR (400 MHz, CDCl3) δ 7.44-7.35 (m, 3H), 7.31-7.26 (m, 2H), 5.66 (d, J=7.33 Hz, 1H), 4.76 (quint, J=7.03 Hz, 1H), 3.04-2.96 (m, 1H), 2.93-2.86 (m, 1H), 1.74-1.66 (m, 1H), 1.52-1.47 (m, 1H), 1.46-1.36 (m, 2H), 1.27-1.16 (m, 2H), 0.92-0.87 (m, 8H); [α]D=+34.1 (cl in CHCl3).

Workup

  1. temperaturethe reaction warmed to room temperature overnight
  2. customThe solvent was evaporated
  3. filtrationfiltered off
  4. washwashed generously with EtOAc
  5. washThe filtrate was washed with water (2×50 mL), and brine
  6. dry with materialThe organics were dried over MgSO4
  7. filtrationfiltered
  8. customThe crude material was chromatographed on silica eluting with 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-ec0e6a3e5ed141e68cc38d25dc33d5ec
Source dataset
uspto-grants-2003_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06620829B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes