Tetrahydrofuran → HCID 11172328, compound

HRID 1784168Notes

Reaction equation

HRID 1784168 reaction equation
[C:1]1([S:7]([C:10]2[C@H](O)C[C@H](C)[CH2:14][CH:15]=2)(=O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:18]CN(CC)CC.CS(Cl)(=O)=O.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:40]1[CH2:44][O:43][CH2:42][CH2:41]1>CC(O)C.C1C=CC=CC=1>[CH3:18][C@H:40]1[CH:41]=[CH:42][C:10]([S:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:15][CH2:14][C@H:44]1[OH:43]

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 71025910HCID 71025910, compound

Product 1

HCID 11172328HCID 11172328, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
0 °C

Procedure

(4S)-4-Methyl-cyclohexa-1,5-dienesulfonyl)-benzene (29z). To a solution of 24z (355 mg, 1.40 mmol) and Et3N (0.19 mL, 1.40 mmol) in THF (10 mL) at 0° C. was added 0.11 mL (1.40 m-mol) of MsCl dropwise. After stirring at 0° C. for 1 h, the reaction mixture was cooled to −78° C., and freshly prepared LiHMDS (2.8 mL, 1.0 M in THF, 2.8 mmol) was added dropwise over 20 min. After stirring at −78° C. for 15 min, the reaction was quenched with saturated aqueous NH4Cl, diluted with ether, separated, further extracted with ether. The organic layers were washed with brine, dried over Na2SO4, and concentrated via rotary evaporation. The crude residue was purified with flash column chromatography (ethyl acetate/hexanes; 1:3) to provide 303 mg (92% yield) of 29 as a white solid with 99% ee by HPLC (Chiralpak AD 1.0 ml/min; 95:5 Hex:2-propanol, 19.57 min for minor enantiomer, 20.51 min for major enantiomer). Mp 54.0-56.0° C.; 1H NMR (CDCl3, 300 MHz): δ 7.85 (m, 2H), 7.48-7.61 (m, 3H), 6.91 (t, J=4.2 Hz, 1H), 6.01 (d, J=10.3 Hz, 1H), 5.81 (dd, J=10.3, 3.9 Hz, 1H), 2.38-2.57 (m, 2H), 2.15 (ddd, J=17.1, 11.1, 4.5 Hz, 1H), 0.98 (d, J=6.6 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ139.9, 138.2, 136.4, 134.5, 133.2, 129.1, 127.6, 117.4, 30.6, 26.9, 19.4. MS(EI) m/z 233 [M−H]+; HRMS (EI) calcd for C13H13O2S, 233.0636; found, 233.0632.

Workup

  1. temperaturethe reaction mixture was cooled to −78° C.
  2. stirringAfter stirring at −78° C. for 15 min
  3. customthe reaction was quenched with saturated aqueous NH4Cl
  4. additiondiluted with ether
  5. customseparated
  6. extractionfurther extracted with ether
  7. washThe organic layers were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated via rotary evaporation
  10. customThe crude residue was purified with flash column chromatography (ethyl acetate/hexanes; 1:3)

Sources & evidence

ORD record
ord-78b524b9b1684a779811e8d7f54e7410
Source dataset
uspto-grants-2009_03
Patent number
US07501535B2

Reaction notes

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