Acetic Acid → HCID 86706131, compound

HRID 2176285Notes

Reaction equation

HRID 2176285 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:11]([C@H:18]1[CH2:22][O:21][C:20](=[O:23])[N:19]1[C:24](=[O:29])[CH2:25][CH:26]1[CH2:28][CH2:27]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1(S(N2C(C3C=CC=CC=3)O2)(=O)=[O:37])C=CC=CC=1.C(O)(=O)C>O1CCCC1>[CH2:11]([C@H:18]1[CH2:22][O:21][C:20](=[O:23])[N:19]1[C:24](=[O:29])[C@H:25]([CH:26]1[CH2:27][CH2:28]1)[OH:37])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 3204052-(Benzenesulfonyl)-3-phenyloxaziridineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 66645641HCID 66645641, compound

Product 1

HCID 86706131HCID 86706131, compoundYield 81.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A cooled (−78° C.) solution of sodium bis(trimethylsilyl)amide (0.6 M in toluene, 65 mL, 38.918 mmol) was diluted with anhydrous tetrahydrofuran (100 mL) and treated with a solution of (S)-4-benzyl-3-(2-cyclopropyl-acetyl)-oxazolidin-2-one (9.174 g, 35.380 mmol) in anhydrous tetrahydrofuran (50 mL). After stirring at −78° C. for 45 min, the mixture was treated with a solution of 2-benzenesulfonyl-3-phenyl-oxaziridine (11.064 g, 42.456 mmol) in anhydrous tetrahydrofuran (50 mL). After stirring at −78° C. for 55 min, the reaction was quenched with acetic acid (10.1 mL, 176.9 mmol) and allowed to warm to room temperature. The mixture was quenched with sodium bicarbonate solution (300 mL) and poured over dichloromethane/iso-hexanes (3:1, 400 mL). The aqueous layer was extracted with dichloromethane and the organics were combined, washed with saturated sodium thiosulfate, hydrochloric acid (1 M, 300 mL), water and filtered through a phase separator. The volatiles were removed in vacuo and the residue was purified by silica gel chromatography using a 100 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 7:3 followed by silica gel chromatography using a 100 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1 to afford the title compound (7.922 g, 81%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.42-0.65 (m, 4H), 1.25-1.38 (m, 1H), 2.88 (dd, J=13.4, 9.6 Hz, 1H), 3.35 (dd, J=13.4, 3.4 Hz, 1H), 3.44 (d, J=8.2 Hz, 1H), 4.25-4.37 (m, 2H), 4.67-4.72 (m, 1H), 4.80 (dd, J=8.0, 6.0 Hz, 1H), 7.21-7.41 (m, 5H). LCMS (m/z) 298.1 [M+Na], Tr=2.27 min.

Workup

  1. stirringAfter stirring at −78° C. for 55 min
  2. temperatureto warm to room temperature
  3. customThe mixture was quenched with sodium bicarbonate solution (300 mL)
  4. additionpoured over dichloromethane/iso-hexanes (3:1, 400 mL)
  5. extractionThe aqueous layer was extracted with dichloromethane
  6. washwashed with saturated sodium thiosulfate, hydrochloric acid (1 M, 300 mL), water
  7. filtrationfiltered through a phase separator
  8. customThe volatiles were removed in vacuo
  9. customthe residue was purified by silica gel chromatography
  10. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 7:3
  11. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 4:1

Sources & evidence

ORD record
ord-839b6c0a8409459dbb580d0aa7b860a5
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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