Sodium hydride → (2R,3S)-3-(4-Methoxyphenyl)oxirane Carboxylic Acid (1R,2S)-2-Phenylcyclohexyl Ester

HRID 1085326Notes

Reaction equation

HRID 1085326 reaction equation
[H-].[Na+].Cl[CH2:4][C:5]([O:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:6].[CH3:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([CH:28]=[O:29])=[CH:26][CH:27]=1>O1CCCC1>[C:14]1([C@@H:9]2[CH2:10][CH2:11][CH2:12][CH2:13][C@H:8]2[O:7][C:5]([C@H:4]2[C@H:28]([C:25]3[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[CH:27][CH:26]=3)[O:29]2)=[O:6])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 312444-MethoxybenzaldehydeHCID 14295383(-)-(1R,2S)-2-phenylcyclohexyl chloroacetate

Product 1

HCID 9841424(2R,3S)-3-(4-Methoxyphenyl)oxirane Carboxylic Acid (1R,2S)-2-Phenylcyclohexyl EsterYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 5.0-L three-necked flask equipped with a stirrer, a gas bubbler, a thermometer, an addition funnel and condenser was charged with 100 g (3.33 mole) of NaH (80% in mineral oil), and triturated with 3×500 mL=1.5 L of hexane. Each portion of hexane was decanted when the NaH had settled. Under an argon atmosphere, 1.5 L of tetrahydrofuran was added followed by a solution of 568 g (2.247 mole) of (-)-(1R,2S)-2-phenylcyclohexyl chloroacetate, 352 g (2.589 mole) of anisaldehyde and 250 mL of tetrahydrofuran over 0.5 hour via addition funnel. A vigorous evolution of H2 gas ensued along with an exotherm to about 55°. After the initial reaction subsided, the mixture was then stirred under argon at ambient temperature overnight. The mixture was heated at 55-60° for 1 hour and then quenched into 8.0 L of ice water. The pH was adjusted to 7 with 390 mL of 3N H2SO4 and the resulting mixture was extracted first with 4 L followed by 2×2 L for a total of 8.0 L of methylene chloride. The combined organic layers were dried (Na2SO4) and evaporated in vacuo to an oily, partially solid residue which on crystallization from 0.5 L of (9:1) hexanes-ethyl acetate afforded colorless needles. These crystals were collected by filtration, washed with 2×200 mL=400 mL of 9:1 hexanes-ethyl acetate followed by 2×500 mL=1.0 L of cold hexanes and finally dried in vacuo to afford 403 g (51%) of the title compound, m.p. 146-148° C., [α]D20 =-146°(c=1; CHC13).

Workup

  1. customA 5.0-L three-necked flask equipped with a stirrer
  2. customtriturated with 3×500 mL=1.5 L of hexane
  3. customEach portion of hexane was decanted when the NaH
  4. additionUnder an argon atmosphere, 1.5 L of tetrahydrofuran was added
  5. customensued along with an exotherm to about 55°
  6. customAfter the initial reaction
  7. temperatureThe mixture was heated at 55-60° for 1 hour
  8. customquenched into 8.0 L of ice water
  9. extractionthe resulting mixture was extracted first with 4 L
  10. dry with materialThe combined organic layers were dried (Na2SO4)
  11. customevaporated in vacuo to an oily, partially solid residue which
  12. customon crystallization from 0.5 L of (9:1) hexanes-ethyl acetate afforded colorless needles
  13. filtrationThese crystals were collected by filtration
  14. washwashed with 2×200 mL=400 mL of 9:1 hexanes-ethyl acetate
  15. customfinally dried in vacuo

Sources & evidence

ORD record
ord-8317bf578c4041a6b260cc728cc6fbea
Source dataset
uspto-grants-1991_04
Patent number
US05008411

Reaction notes

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