Acetic Acid → (R)-3-((R)-6-(4-fluoro-3-methylbenzyloxy)-2-azidohexanoyl)-4-benzyloxazolidin-2-one

HRID 885513Notes

Reaction equation

HRID 885513 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:11][C:12]1[CH:39]=[CH:38][C:15]([CH2:16][O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([N:25]2[C@H:29]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:28][O:27][C:26]2=[O:37])=[O:24])=[CH:14][C:13]=1[CH3:40].CC(C1C=C(C(C)C)C(S([N:56]=[N+:57]=[N-:58])(=O)=O)=C(C(C)C)C=1)C.CC(O)=O>C1COCC1.[Cl-].[Na+].O>[F:11][C:12]1[CH:39]=[CH:38][C:15]([CH2:16][O:17][CH2:18][CH2:19][CH2:20][CH2:21][C@@H:22]([N:56]=[N+:57]=[N-:58])[C:23]([N:25]2[C@H:29]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:28][O:27][C:26]2=[O:37])=[O:24])=[CH:14][C:13]=1[CH3:40]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3717072,4,6-Triisopropylbenzenesulfonyl azideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 59512592(R)-3-(6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-one

Product 1

HCID 86667071(R)-3-((R)-6-(4-fluoro-3-methylbenzyloxy)-2-azidohexanoyl)-4-benzyloxazolidin-2-oneYield 48%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.) solution of KHMDS (3.49 mL, 1.745 mol, 0.5 M in toluene) in 5 mL of THF was added a cooled (−78° C.) solution of (R)-3-(6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-one (0.481 g, 1.163 mmol) in 4 mL of THF. The reaction was stirred at −78° C. under N2 for 1 h. Then a cooled (−78° C.) solution of trisyl azide (0.448 g, 1.454 mmol) in 4 mL of THF was added. After 1-2 min, a solution of HOAc (0.321 g, 5.350 mmol) in 4 mL of THF was added. After warmed slowly to room temperature and stirred for overnight, the reaction mixture was diluted with brine (50 mL) and extracted with dichloromethane (40 mL×3). The combined organic extracts dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-100% dichloromethane/hexanes to give the title compound as colorless oil (0.252 g, 48% yield). FT-IR (neat): 2104, 1778, 1704 cm−1.

Workup

  1. additionwas added
  2. additionwas added
  3. waitAfter 1-2 min
  4. temperatureAfter warmed slowly to room temperature
  5. stirringstirred for overnight
  6. extractionextracted with dichloromethane (40 mL×3)
  7. dry with materialThe combined organic extracts dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe product was isolated by Flash column chromatography (silica gel column)
  11. washeluting with 0-100% dichloromethane/hexanes

Sources & evidence

ORD record
ord-bb5149f2eabf41d698e994bcdb66de6c
Source dataset
uspto-grants-2012_08
Patent number
US08242174B2

Reaction notes

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