Hydrochloric Acid → ethyl 3-[(4S,5S)-3-benzyloxycarbonyl-2,2-dimethyl-4-isobutyloxazolidine-5-yl]-2-[3-(2-tetrahydropyranyloxy)propyl]-2-propenoate

HRID 232125Notes

Reaction equation

HRID 232125 reaction equation
[Cl-].[Li+].C(OP([CH:11]([CH2:17][CH2:18][CH:19]([O:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][O:24]1)CC)[C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.C1(C2CCCCCCCCCC=2)CCCCCCCCNN=1.[CH2:51]([O:58][C:59]([N:61]1[C@@H:65]([CH2:66][CH:67]([CH3:69])[CH3:68])[C@H:64]([CH:70]=O)[O:63][C:62]1([CH3:73])[CH3:72])=[O:60])[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.Cl>O1CCCC1>[CH2:51]([O:58][C:59]([N:61]1[C@@H:65]([CH2:66][CH:67]([CH3:68])[CH3:69])[C@H:64]([CH:70]=[C:11]([CH2:17][CH2:18][CH2:19][O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[O:63][C:62]1([CH3:72])[CH3:73])=[O:60])[C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 433294Lithium ChlorideHCID 14649485(4S,5R)-3-benzyloxycarbonyl-2,2-dimethyl-5-formyl-4-isobutyloxazolidineHCID 20030536Ethyl 2-diethylphosphono-5-(2-tetrahydropyranyloxy)heptanoateHCID 536302743-(Cycloundecen-1-yl)-1,2-diazacycloundec-2-ene

Product 1

HCID 70046087ethyl 3-[(4S,5S)-3-benzyloxycarbonyl-2,2-dimethyl-4-isobutyloxazolidine-5-yl]-2-[3-(2-tetrahydropyranyloxy)propyl]-2-propenoateYield 84.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
0 °C

Procedure

63.4 mg of lithium chloride was suspended in 5 ml of dry tetrahydrofuran under an argon gas stream. A solution prepared by dissolving 546 mg of ethyl 2-diethylphosphono-5-(2-tetrahydropyranyloxy)heptanoate in 0.6 ml of dry tetrahydrofuran, was added thereto under stirring. The mixture was stirred for five minutes at room temperature, and then 1.4 ml of a 20% dry tetrahydrofuran solution of diazabicycloundecene was added. The mixture was stirred for 10 minutes at room temperature. Then, a solution prepared by dissolving 396 mg of (4S,5R)-3-benzyloxycarbonyl-2,2-dimethyl-5-formyl-4-isobutyloxazolidine in 1.0 ml of dry tetrahydrofuran, was added thereto, and the mixture was stirred overnight at room temperature. The mixture was cooled to 0° C. and then neutralized with 1N hydrochloric acid. Insolubles were filtered off, and the solvent was distilled off under reduced pressure. The residue was dissolved in 20 ml of ethyl acetate and washed with water. The aqueous layer was further extracted twice with 15 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (8 g of Kieselgel 60) by using a mixture of hexane/ethyl acetate (10/1) to obtain 556 mg of ethyl 3-[(4S,5S)-3-benzyloxycarbonyl-2,2-dimethyl-4-isobutyloxazolidine- 5-yl]-2-[3-(2-tetrahydropyranyloxy)propyl]-2-propenoate (E/Z (60/40)) as a colorless oily substance.

Workup

  1. customA solution prepared
  2. additionwas added
  3. stirringThe mixture was stirred for five minutes at room temperature
  4. stirringThe mixture was stirred for 10 minutes at room temperature
  5. customThen, a solution prepared
  6. additionwas added
  7. stirringthe mixture was stirred overnight at room temperature
  8. filtrationInsolubles were filtered off
  9. distillationthe solvent was distilled off under reduced pressure
  10. dissolutionThe residue was dissolved in 20 ml of ethyl acetate
  11. washwashed with water
  12. extractionThe aqueous layer was further extracted twice with 15 ml of ethyl acetate
  13. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  14. distillationThe solvent was distilled off under reduced pressure
  15. customthe residue was purified by silica gel column chromatography (8 g of Kieselgel 60)
  16. additiona mixture of hexane/ethyl acetate (10/1)

Sources & evidence

ORD record
ord-8628a368a02947538f088e7553e7a5e2
Source dataset
uspto-grants-1989_07
Patent number
US04851387

Reaction notes

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