Tetrahydrofuran → HCID 72472351, compound

HRID 564354Notes

Reaction equation

HRID 564354 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]23[CH2:26][CH2:25][CH:24]([S:27]C(=O)C)[CH2:23][CH:12]2[CH2:13][O:14][C:15]2[C:20]3=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[F:22])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[OH-].[Na+].C1COCC1>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([C:11]23[CH2:26][CH2:25][CH:24]([SH:27])[CH2:23][CH:12]2[CH2:13][O:14][C:15]2[C:20]3=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[F:22])(=[O:10])=[O:9])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 72472370HCID 72472370, compound

Product 1

HCID 72472351HCID 72472351, compoundYield 34.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of thioacetic acid S-[10a-(4-chloro-benzenesulfonyl)-1,4-difluoro-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-8-yl]ester (420 mg, 0.888 mmol) in MeOH (8 mL) was treated with 1N NaOH (2 mL) followed by THF (3 mL). After 4 h, the reaction mixture was concentrated in vacuo, diluted with 1N HCl and extracted with EtOAc (2×). The combined organic extracts were washed with saturated aqueous NaHCO3, brine, dried over MgSO4 and concentrated in vacuo. Flash chromatography (2→20% EtOAc/Hex) gave the disulfide of the title compound (133 mg, 17%): 1H NMR (CDCl3 400 MHz) δ 7.62 (d, J=8.8 Hz, 4H), 7.51 (d, J=8.8 Hz, 4H), 7.07 (m, 2H), 6.41 (m, 2H), 5.24 (dd, J=11.0, 2.9 Hz, 2H), 4.11 (d, J=11.0 Hz, 2H), 3.48 (m, 2H), 3.14 (d, J=13.2 Hz, 2H), 2.55 (m, 2H), 2.42 (m, 2H), 1.92-1.52 (m, 8H); followed by the title compound (169 mg, 44%): 1H NMR (CDCl3 400 MHz) δ 7.60 (dd, J=8.8, 1.5 Hz, 2H), 7.48 (dd, J=8.8, 1.5 Hz, 2H), 7.08 (m, 1H), 6.42 (m, 1H), 5.25 (dd, J=11.7, 2.2 Hz, 1H), 4.11 (d, J=11.0 Hz, 1H), 3.11 (m, 1H), 2.95 (d, J=12.5 Hz, 1H), 2.40-2.38 (m, 2H), 2.04-1.82 (m, 3H), 1.49 (m, 1H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. additiondiluted with 1N HCl
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic extracts were washed with saturated aqueous NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a02ac28173a9425b97094f1f4e123496
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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