Ammonium Chloride → (R)-4-Isopropyl-3-((R)-2-methoxymethyl-2-methyl-but-3-enoyl)-oxazolidin-2-one

HRID 2285403Notes

Reaction equation

HRID 2285403 reaction equation
[OH:1][CH2:2][C@@:3]([CH3:17])([CH:15]=[CH2:16])[C:4]([N:6]1[C@H:10]([CH:11]([CH3:13])[CH3:12])[CH2:9][O:8][C:7]1=[O:14])=[O:5].[CH3:18]N(C)C1C2C(=CC=CC=2N(C)C)C=CC=1.F[B-](F)(F)F.C[O+](C)C.[Cl-].[NH4+]>ClCCl>[CH:11]([C@@H:10]1[CH2:9][O:8][C:7](=[O:14])[N:6]1[C:4](=[O:5])[C@:3]([CH2:2][O:1][CH3:18])([CH3:17])[CH:15]=[CH2:16])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 88675Proton spongeHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 86709685(R)-3-((R)-2-Hydroxymethyl-2-methyl-but-3-enoyl)-4-isopropyl-oxazolidin-2-one

Product 1

HCID 86709698(R)-4-Isopropyl-3-((R)-2-methoxymethyl-2-methyl-but-3-enoyl)-oxazolidin-2-oneYield 34.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (R)-3-((R)-2-hydroxymethyl-2-methyl-but-3-enoyl)-4-isopropyl-oxazolidin-2-one (724 mg, 3.00 mmol) and N,N,N′,N′-tetramethyl-1,8-naphthalenediamine (2.57 g, 11.0 mmol) in dichloromethane (15 mL) at 0° C. under nitrogen was added trimethyloxonium tetrafluoroborate (1.33 g, 9.00 mmol). The reaction was stirred at 0° C. for 15 minutes and then 4.5 h at ambient temperature. Saturated ammonium chloride solution was added and the mixture diluted with dichloromethane. The aqueous layer was separated and extracted with dichloromethane and the combined organic extracts washed with ammonium chloride solution, dried over anhydrous sodium sulfate filtered and evaporated. The residue was suspended in diethyl ether and filtered, the solids were washed with diethyl ether and the filtrate evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 1:0 to 4:1 followed by purification on an SCX cartridge eluting with methanol to give the title compound (263 mg, 34%) as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 0.91 (app t, J=7.0 Hz, 6H), 1.50 (s, 3H), 2.32-2.43 (m, 1H), 3.35 (s, 3H), 3.46 (d, J=8.7 Hz, 1H), 4.19 (app dd, J=9.1, 3.6 Hz, 1H), 4.27 (app t, J=8.6 Hz, 1H), 4.50-4.57 (m, 1H), 5.00 (d, J=17.9 Hz, 1H), 5.12 (d, J=10.7 Hz, 1H), 6.19 (dd, J=17.9, 10.7 Hz, 1H). LCMS (m/z) 256.2 [M+H], Tr=2.53 min.

Workup

  1. custom4.5 h
  2. customat ambient temperature
  3. customThe aqueous layer was separated
  4. extractionextracted with dichloromethane
  5. washthe combined organic extracts washed with ammonium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. filtrationfiltered
  10. washthe solids were washed with diethyl ether
  11. customthe filtrate evaporated
  12. customThe residue was purified by silica gel chromatography
  13. customfollowed by purification on an SCX cartridge
  14. washeluting with methanol

Sources & evidence

ORD record
ord-e204ba8735d04da681297ea7c6d0b640
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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