Cyclopentanone → (2R,5S)-2-t-Butyl-5-(1-hydroxycyclopentyl)-5-phenyl-1,3-dioxolan-4-one

HRID 220325Notes

Reaction equation

HRID 220325 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:11]([C@H:15]1[O:19][C:18](=[O:20])[C@@H:17]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:16]1)([CH3:14])([CH3:13])[CH3:12].[C:27]1(=[O:32])[CH2:31][CH2:30][CH2:29][CH2:28]1.[Cl-].[NH4+]>C1COCC1>[C:11]([C@H:15]1[O:19][C:18](=[O:20])[C@@:17]([C:27]2([OH:32])[CH2:31][CH2:30][CH2:29][CH2:28]2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:16]1)([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 8452CyclopentanoneHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 110094971,3-Dioxolan-4-one, 2-(1,1-dimethylethyl)-5-phenyl-, (2R,5R)-

Product 1

HCID 11695185(2R,5S)-2-t-Butyl-5-(1-hydroxycyclopentyl)-5-phenyl-1,3-dioxolan-4-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Lithium hexamethyldisilazide (0.8 g, 4.7 mmol; 4.7 mL of 1.0 M in hexanes) was added to anhydrous THF (5.3 mL, 65 mmol) at −78° C. Intermediate (1a) (800 mg, 3.6 mmol) in 5.3 mL anhydrous THF was added to the solution dropwise over 15 minutes. After 30 minutes cyclopentanone (451 μL, 5.1 mmol) was added dropwise over less than 1 minute. After 2 hours, 0.8 mL of saturated aqueous Na2HPO4 was added, and the mixture stirred at room temperature for 5 minutes. The mixture was added to 8 mL saturated aqueous ammonium chloride. The aqueous layer was washed (2×80 mL EtOAc), and the organic layers were combined, dried over Na2SO4, filtered, and concentrated. The crude product (780 mg) was purified by flash chromatography (5-15% EtOAc gradient over 30 minutes with hexanes) to yield intermediate (1b).

Workup

  1. washThe aqueous layer was washed (2×80 mL EtOAc)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product (780 mg) was purified by flash chromatography (5-15% EtOAc gradient over 30 minutes with hexanes)

Sources & evidence

ORD record
ord-6b76d8c811a84ca3b606df4226bf5d03
Source dataset
uspto-grants-2012_06
Patent number
US08202891B2

Reaction notes

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