Acetic Acid → tert-butyl (E)-(2S,3S)-2-hydroxy-3-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidine-3-carbonyl)-2-propyl-10-(2-trimethylsilanyl-ethoxycarbonylamino)-dec-4-enoate

HRID 1779227Notes

Reaction equation

HRID 1779227 reaction equation
[CH:1]([C@H:4]1[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[O:7][C:6](=[S:21])[N:5]1[C:22](=[O:41])[CH2:23]/[CH:24]=[CH:25]/[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:40])[O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])([CH3:3])[CH3:2].[Cl-].[Li+].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[O:54]=[C:55]([CH2:63][CH2:64][CH3:65])[C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57].C(O)(=O)C>O1CCCC1>[OH:54][C@@:55]([CH2:63][CH2:64][CH3:65])([C@@H:23]([C:22]([N:5]1[C@@H:4]([CH:1]([CH3:3])[CH3:2])[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[O:7][C:6]1=[S:21])=[O:41])/[CH:24]=[CH:25]/[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32]([O:33][CH2:34][CH2:35][Si:36]([CH3:37])([CH3:39])[CH3:38])=[O:40])[C:56]([O:58][C:59]([CH3:61])([CH3:60])[CH3:62])=[O:57]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 433294Lithium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 13237359tert-Butyl 2-oxopentanoateHCID 900602442-trimethylsilanyl-ethyl [(E)-9-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-9-oxo-non-6-enyl]-carbamate

Product 1

HCID 90060242tert-butyl (E)-(2S,3S)-2-hydroxy-3-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidine-3-carbonyl)-2-propyl-10-(2-trimethylsilanyl-ethoxycarbonylamino)-dec-4-enoateYield 52.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

2-Trimethylsilanyl-ethyl [(E)-9-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidin-3-yl)-9-oxo-non-6-enyl]-carbamate (400 mg, 0.672 mmol) and dried lithium chloride (114 mg, 2.69 mmol) were dissolved in tetrahydrofuran (3.2 mL), and the mixture was then cooled to −78° C. in a dry ice-acetone bath. Lithium hexamethyldisilazide (a solution of 1 M tetrahydrofuran, 1.51 mL, 1.51 mmol) was added in order, and the mixture was then stirred for 1 hour. A solution of tert-butyl 2-oxo-pentanoate (130 mg, 0.755 mmol) in tetrahydrofuran (2.4 mL) was added, and the mixture was then stirred at −78° C. for further 6 hours, and quenched with acetic acid (0.160 mL, 2.80 mmol). The dry ice-acetone bath was then removed. Ethyl acetate (30 mL) and water (10 mL) were added and the mixture was then separated. The organic layer was washed with a saturated aqueous solution (20 mL) of sodium chloride, then dried over anhydrous sodium sulfate, and filtered. The solvent was then distilled off under reduced pressure. The residue was purified on Biotage (silica gel, n-hexane/ethyl acetate) to obtain 270 mg (0.352 mmol, 52% yield) of tert-butyl (E)-(2S,3S)-2-hydroxy-3-((S)-4-isopropyl-5,5-diphenyl-2-thioxo-oxazolidine-3-carbonyl)-2-propyl-10-(2-trimethylsilanyl-ethoxycarbonylamino)-dec-4-enoate.

Workup

  1. stirringthe mixture was then stirred at −78° C. for further 6 hours
  2. customThe dry ice-acetone bath was then removed
  3. additionEthyl acetate (30 mL) and water (10 mL) were added
  4. customthe mixture was then separated
  5. washThe organic layer was washed with a saturated aqueous solution (20 mL) of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. distillationThe solvent was then distilled off under reduced pressure
  9. customThe residue was purified on Biotage (silica gel, n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-f73bb86253fd48a78209ea66e543f799
Source dataset
uspto-grants-2016_02
Patent number
US09266853B2

Reaction notes

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