Trifluoroacetic acid → HCID 58975195, compound

HRID 736985Notes

Reaction equation

HRID 736985 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]([C:22]3(O)[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]([CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:14]2)(=[O:11])=[O:12])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58975212HCID 58975212, compound

Product 1

HCID 58975195HCID 58975195, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add to a solution of 4-[3-(4-hydroxy-tetrahydro-pyran-4-yl)-indole-1-sulfonyl]-benzoic acid methyl ester (20.0 g, 48.19 mmol) in anhydrous methylene chloride (500 mL) at room temperature, triethylsilane (20.0 mL, 125.19 mmol) and trifluoroacetic acid (61.5 mL, 798.2 mmol). Stir the resulting solution for 1 h, concentrate, and obtain the oil and partition between ethyl acetate (500 mL) and saturated sodium bicarbonate (500 mL). Dry the organic layer over sodium sulfate, filter through a silica gel pad, and back-wash with ethyl acetate (400 mL). Concentrate the filtrate to low volume, add hexanes, and a separate the solid. Filter the solid and hold aside, 14 g. Concentrate the filtrate to low volume and add MTBE to provide a second crop of crystals, filter and found identical by TLC (3:2 hexanes/ethyl acetate) to the original lot, 2.8 g. Combine the two lots and dry (20 mmg Hg, 40° C.) to provide one lot of highly pure title compound for subsequent hydrolysis (16.8 g, 87%); 1H NMR (DMSO-d6) δ 8.10 (m, 4H), 7.93 (d, J=8.2 Hz, 1H), 7.68 (d, J=7.7 Hz, 1H), 7.57 (s, 1H), 7.37 (t, J=7.7 Hz, 1H), 7.28 (t, J=7.1 Hz, 1H), 3.94 (m, 2H), 3.85 (s, 3H), 3.50 (t, J=11.5 Hz, 2H), 3.03 (m, 1H), 1.86 (m, 2H), 1.70 (m, 2H); MS (ESI) m/z 400 (m+H).

Workup

  1. concentrationconcentrate
  2. customobtain the oil
  3. custompartition between ethyl acetate (500 mL) and saturated sodium bicarbonate (500 mL)
  4. dry with materialDry the organic layer over sodium sulfate
  5. filtrationfilter through a silica gel pad
  6. washback-wash with ethyl acetate (400 mL)
  7. concentrationConcentrate the filtrate to low volume
  8. additionadd hexanes
  9. customa separate the solid
  10. filtrationFilter the solid
  11. concentrationConcentrate the filtrate to low volume
  12. additionadd MTBE
  13. customto provide a second crop of crystals
  14. filtrationfilter
  15. customdry (20 mmg Hg, 40° C.)

Sources & evidence

ORD record
ord-fcd3ebe091764ca6b8d5dfcb5af8354e
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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