Hydrogen Peroxide → HCID 178462222, compound

HRID 2285396Notes

Reaction equation

HRID 2285396 reaction equation
[C:1]([SiH2:5][O:6][C:7]([CH3:37])([CH3:36])[C@@:8](C)(/[CH:20]=[CH:21]/[C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][C:26]([C@H:32]([OH:34])[CH3:33])=[CH:27][CH:28]=2)[CH:23]=1)[C:9](N1[C@H](C(C)C)COC1=O)=O)([CH3:4])([CH3:3])[CH3:2].[OH:38]O.O.[OH-].[Li+].[O:43]1[CH2:47]CCC1.O>>[C:1]([SiH2:5][O:6][C:7]([CH3:36])([CH3:37])[C@@:8]([CH3:9])(/[CH:20]=[CH:21]/[C:22]1[CH:23]=[CH:24][C:29]2[C:30](=[CH:25][C:26]([C@H:32]([OH:34])[CH3:33])=[CH:27][CH:28]=2)[CH:31]=1)[C:47]([OH:43])=[O:38])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 784Hydrogen Peroxide2×HCID 168937Lithium hydroxide, monohydrate2×HCID 21881883Oxolane--water (1/1)HCID 178448164HCID 178448164, compound

Product 1

HCID 178462222HCID 178462222, compoundYield 84%

Conditions

Temperature
0 °C

Procedure

A cooled (0° C.) solution of (R)-3-{(E)-(R)-2-(tert-butyl-dimethyl-silanyloxymethyl)-4-[7-((R)-1-hydroxy-ethyl)-naphthalen-2-yl]-2-methyl-but-3-enoyl}-4-isopropyl-oxazolidin-2-one (116.7 mg, 0.222 mmol) in tetrahydrofuran/water (12 mL, 5:1) was subsequently treated with hydrogen peroxide (30% aqueous, 120 μL, 1.110 mmol) and lithium hydroxide monohydrate (18.6 mg, 0.444 mmol). After stirring at 0° C. for 3.5 h, the reaction mixture was treated with hydrogen peroxide (30% aqueous, 120 μL, 1.110 mmol) and lithium hydroxide monohydrate (18.6 mg, 0.444 mmol). After stirring at 0° C. for 2.5 h the reaction was quenched with solid sodium metabisulfite (850 mg). After stirring at room temperature for 45 mins the mixture was acidified with hydrochloric acid (1 M, 20 mL). The aqueous layer was extracted with dichloromethane (2×). The combined organics were filtered through a phase separator and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 25 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 3:2 to afford the title compound (77.1 mg, 84%) as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 0.15 (s, 6H), 0.94 (s, 9H), 1.47 (s, 3H), 1.60 (d, J=6.5 Hz, 3H), 3.79, 3.92 (ABq, JAB=9.6 Hz, 2H), 5.08 (q, J=6.5 Hz, 1H), 6.43 (d, J=16.5 Hz, 1H), 6.72 (d, J=16.5 Hz, 1H), 7.06-7.22 (m, 2H), 7.40-7.60 (m, 2H), 7.70-7.84 (m, 2H). LCMS (m/z) 415.2 [M+H], Tr=3.40 min.

Workup

  1. stirringAfter stirring at 0° C. for 2.5 h the reaction
  2. customwas quenched with solid sodium metabisulfite (850 mg)
  3. stirringAfter stirring at room temperature for 45 mins the mixture
  4. extractionThe aqueous layer was extracted with dichloromethane (2×)
  5. filtrationThe combined organics were filtered through a phase separator
  6. customthe volatiles were removed in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 3:2

Sources & evidence

ORD record
ord-0d580087aea24e65a26457854de8ae62
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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