2,6-Lutidine → (3R,4R,5S)-5-methyl-3-phenethyl-4-((triisopropyl-silyl)oxy)dihydrofuran-2(3H)-one

HRID 58953

Reaction equation

HRID 58953 reaction equation
[OH:1][C@H:2]1[C@H:6]([CH3:7])[O:5][C:4](=[O:8])[C@@H:3]1[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CC1C=CC=C(C)N=1.FC(F)(F)S(O[Si:31]([CH:38]([CH3:40])[CH3:39])([CH:35]([CH3:37])[CH3:36])[CH:32]([CH3:34])[CH3:33])(=O)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:7][C@@H:6]1[O:5][C:4](=[O:8])[C@H:3]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@H:2]1[O:1][Si:31]([CH:38]([CH3:40])[CH3:39])([CH:35]([CH3:37])[CH3:36])[CH:32]([CH3:34])[CH3:33]

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 516892Sodium BicarbonateHCID 2724529Triisopropylsilyl trifluoromethanesulfonateHCID 117974545(3R,4R,5S)-4-hydroxy-5-methyl-3-phenethyldihydrofuran-2(3H)-one

Product 1

HCID 123299646(3R,4R,5S)-5-methyl-3-phenethyl-4-((triisopropyl-silyl)oxy)dihydrofuran-2(3H)-oneYield 59.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3R,4R,5S)-4-hydroxy-5-methyl-3-phenethyldihydrofuran-2(3H)-one (800 mg, 3.63 mmol) in CH2Cl2 (20 mL) were added 2,6-dimethylpyridine (592 μl, 5.08 mmol) and triisopropylsilyl trifluoromethanesulfonate (1171 μL, 4.36 mmol) at 0° C., and the mixture was warmed to room temperature while stirring overnight. The reaction mixture was poured onto 50 mL saturated sodium bicarbonate solution and mixed thoroughly. The phases were separated, and the aqueous extracted with CH2Cl2 (2×25 mL). The combined CH2Cl2 extracts were dried and concentrated to a colorless oil which was purified by flash chromatography (SiO2, 0→50% EtOAc/hexanes) to give (3R,4R,5S)-5-methyl-3-phenethyl-4-((triisopropylsilyl)oxy)dihydro-furan-2(3H)-one (809 mg, 53%): 1H NMR (400 MHz, CDCl3) δ 7.33-7.25 (m, 2H), 7.25-7.17 (m, 3H), 3.98 (dd, J=5.9, 4.8 Hz, 1H), 4.34-4.24 (m, 1H), 2.99-2.88 (m, 1H), 2.88-2.76 (m, 1H), 2.61-2.51 (m, 1H), 2.04-1.94 (m, 2H), 1.43 (d, J=6.5 Hz, 3H), 1.09-0.99 (m, 21H); 13C NMR (101 MHz, CDCl3) δ 176.64, 140.98, 128.57, 128.51, 126.16, 82.10, 79.45, 49.17, 32.96, 31.14, 19.10, 18.00, 17.71; ESIMS m/z 378 ([M+H]+).

Workup

  1. additionmixed thoroughly
  2. customThe phases were separated
  3. extractionthe aqueous extracted with CH2Cl2 (2×25 mL)
  4. dry with materialThe combined CH2Cl2 extracts were dried
  5. concentrationconcentrated to a colorless oil which
  6. customwas purified by flash chromatography (SiO2, 0→50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5927ef077ffa469daf0c8d4bc94ff615
Source dataset
uspto-grants-2016_09
Patent number
US09439422B2

Linked notes

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