Lithium Hexamethyldisilazide → (R)-3-((S)-2-(4-fluoro-3,5-dimethylbenzyl)-6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-one

HRID 1158134Notes

Reaction equation

HRID 1158134 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([N:15]2[C@H:19]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:18][O:17][C:16]2=[O:27])=[O:14])=[CH:4][C:3]=1[CH3:30].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:41][C:42]1[CH:43]=[C:44]([CH:47]=[C:48]([CH3:51])[C:49]=1[F:50])[CH2:45]Br>C1COCC1>[F:50][C:49]1[C:48]([CH3:51])=[CH:47][C:44]([CH2:45][C@H:12]([CH2:11][CH2:10][CH2:9][CH2:8][O:7][CH2:6][C:5]2[CH:28]=[CH:29][C:2]([F:1])=[C:3]([CH3:30])[CH:4]=2)[C:13]([N:15]2[C@H:19]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:18][O:17][C:16]2=[O:27])=[O:14])=[CH:43][C:42]=1[CH3:41]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 177507135-(Bromomethyl)-2-fluoro-1,3-dimethylbenzeneHCID 59512592(R)-3-(6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-one

Product 1

HCID 59512593(R)-3-((S)-2-(4-fluoro-3,5-dimethylbenzyl)-6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-oneYield 36.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.) solution of (R)-3-(6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-one (0.220 g, 0.532 mmol) in 5 mL of THF, was added LiHMDS (0.80 mL, 0.80 mmol, 1.0 M in THF). The resulting mixture was stirred at −78° C. under N2 for 1 h and then a solution of 3,5-dimethyl-4-fluorobenzyl bromide (0.346 g, 1.596 mmol) in 3 mL of THF was added. After stirring at −78° C. for 1 h the reaction mixture was warmed to room temperature for 2 h, and then quenched with 20 mL of NH4Cl solution and extracted with dichloromethane (20 mL×3). The combined organic extracts were 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 (0.106 g, 36% yield). GC-MS: tR=15.6 min; m/z 549 (M+).

Workup

  1. stirringAfter stirring at −78° C. for 1 h the reaction mixture
  2. temperaturewas warmed to room temperature for 2 h
  3. customquenched with 20 mL of NH4Cl solution
  4. extractionextracted with dichloromethane (20 mL×3)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was isolated by Flash column chromatography (silica gel column)
  9. washeluting with 0-100% dichloromethane/hexanes

Sources & evidence

ORD record
ord-a491f174b7ee4f6b9405241b3efff509
Source dataset
uspto-grants-2010_10
Patent number
US07807720B2

Reaction notes

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