Tetrahydrofuran → HCID 10341534, compound

HRID 1784162Notes

Reaction equation

HRID 1784162 reaction equation
[C:1]1([S:7]([C:10]2[C@H:17]3[C@H:15]([O:16]3)[C@H:14]([CH3:18])[C@H:13]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[C@@H:12]([CH3:27])[CH:11]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1COCC1.CC(C[AlH]CC(C)C)C>C1(C)C=CC=CC=1>[C:1]1([S:7]([C:10]2[CH2:17][C@H:15]([OH:16])[C@H:14]([CH3:18])[C@H:13]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:21])[CH3:22])[C@@H:12]([CH3:27])[CH:11]=2)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14487Diisobutylaluminum hydrideHCID 10070049HCID 10070049, compound

Product 1

HCID 10341534HCID 10341534, compoundYield 87.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

Compound α37 (39 mg, 0.095 mmol) was dissolved in dry toluene (1.0 mL), and the temperature lowered to −78° C. To this cold solution was added THF (10 μL, 0.12 mmol), followed by DIBAL-H solution (0.20 mL of 1.55M in toluene) under nitrogen, and the reaction stirred magnetically at −78° C. for 3 hours. Upon completion, the reaction was quenched by 5% HCl aqueous solution, and extracted with ethyl acetate (3×5 mL). The organic layers were combined and washed with brine, and dried over anhydrous Na2SO4. The crude reaction mixture was purified by flash column chromatography (ethyl acetate/hexanes; 1:3) to afford 34 mg (85%) of a mixture (1,2 vs 1,4-reduction; 4.5:1). 13 mg (35%) of pure 60 was obtained via flash column chromatography eluting with CH2Cl2: CH3CN (25:1). [α]20D=−77.7 (c=0.65, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 7.87-7.91 (m, 2H), 7.49-7.63 (m, 3H), 7.31 (br d, J=8.4 Hz, 1H), 3.80 (d, J=5.1 Hz, 1H), 3.66 (m, 1H), 3.32 (d, J=9.3 Hz, 1H), 2.94 (m, 2H), 2.57 (dt, J=16.5 Hz, 2.1 Hz, 1H), 1.98 (m, 1H), 1.18 (d, J=7.2 Hz, 3H), 1.13 (d, J=7.2 Hz, 3H), 0.88 (s, 9H), 0.14 (s, 3H), 0.10 (s, 3H); 13C NMR (C6D6, 75 MHz) δ 143.1, 140.4, 138.9, 133.5, 129.1, 128.8, 79.6, 71.0, 39.6, 38.0, 34.4, 25.9, 18.2, 18.0, 15.0, −4.4, −4.8; LRMS (CI): m/z 411 [M+H]+; HRMS (CI) calculated for C21H35O4SSi, 411.2025; found, 411.2025

Workup

  1. customlowered to −78° C
  2. customUpon completion, the reaction was quenched by 5% HCl aqueous solution
  3. extractionextracted with ethyl acetate (3×5 mL)
  4. washwashed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. customThe crude reaction mixture
  7. customwas purified by flash column chromatography (ethyl acetate/hexanes; 1:3)

Sources & evidence

ORD record
ord-39222e8f250c4a279aec2e928411e88c
Source dataset
uspto-grants-2009_03
Patent number
US07501535B2

Reaction notes

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