Acetic Acid → HCID 86751960, compound

HRID 726752Notes

Reaction equation

HRID 726752 reaction equation
C([Li])CCC.C(S)CC.[CH:10]1([O:15][C:16]2[CH:17]=[C:18]([C@@H:24]([C:48]3[CH:53]=[CH:52][C:51]([C:54]([O:63][CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])([C:59]([F:62])([F:61])[F:60])[C:55]([F:58])([F:57])[F:56])=[CH:50][CH:49]=3)[CH:25]([C:42]3[CH:47]=[CH:46][N:45]=[CH:44][CH:43]=3)C(N3[C@H]4CC5C(C)(C)[C@@]4(CC5)CS3(=O)=O)=O)[CH:19]=[CH:20][C:21]=2[O:22][CH3:23])[CH2:14][CH2:13][CH2:12][CH2:11]1.O.[OH-].[Li+].CC(O)=O>C1COCC1.O>[CH:10]1([O:15][C:16]2[CH:17]=[C:18]([C@@H:24]([C:48]3[CH:53]=[CH:52][C:51]([C:54]([O:63][CH2:64][O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])([C:55]([F:56])([F:57])[F:58])[C:59]([F:62])([F:61])[F:60])=[CH:50][CH:49]=3)[CH2:25][C:42]3[CH:43]=[CH:44][N:45]=[CH:46][CH:47]=3)[CH:19]=[CH:20][C:21]=2[O:22][CH3:23])[CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 7848Propyl mercaptanHCID 168937Lithium hydroxide, monohydrateHCID 86751961HCID 86751961, compoundHCID 178418339Butyllithium

Product 1

HCID 86751960HCID 86751960, compoundYield 58.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (2.4M solution in hexane; 7.76 mL, 18.6 mmol) was added dropwise to a solution of 1-propanethiol (2.06 mL, 22.8 mmol) in THF (100 mL) at 0° C. After 1.5 h, a solution of (1R, 5S)-N-{(3R)-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-[4-(2-(2-(trimethylsilyl)ethoxymethoxy)-1,1,1,3,3,3-hexafluoropropan-2-yl)phenyl]-2-(4-pyridyl)propanoyl}-10,10-dimethyl-3-thia-4-azatricyclo[5.2.1.01,5 ]decane-3,3-dioxide from Step 3 (9.43 g, 10.4 mmol) in THF (25 mL) was added dropwise, at 0° C., and the reaction mixture was stirred at room temperature for 3 h. The reaction was then quenched by the addition of 25% aqueous NH4OAc buffer. The aqueous layer was extracted with EtOAc (2×), and the combined organics were washed successively with 25% aqueous NH4OAc buffer and brine, dried (MgSO4) and concentrated. The residue was dissolved in EtOH (170 mL) and water (57 mL), lithium hydroxide monohydrate (2.20 g, 52.0 mmol) was added and the mixture heated to reflux for 2.5 h. The reaction mixture was cooled to room temperature before the addition of AcOH (3.56 mL, 62.1 mmol). After 30 min., 25% aqueous NH4OAc buffer was added and the aqueous layer extracted with EtOAc (2×). The combined organics were washed successively with 25% aqueous NH4OAc buffer and brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography on silica (EtOAc/hexane 1:1) to afford the title compound as a colorless gum (4.08 g, 58%).

Workup

  1. customThe reaction was then quenched by the addition of 25% aqueous NH4OAc buffer
  2. extractionThe aqueous layer was extracted with EtOAc (2×)
  3. washthe combined organics were washed successively with 25% aqueous NH4OAc buffer and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in EtOH (170 mL)
  7. temperaturethe mixture heated
  8. temperatureto reflux for 2.5 h
  9. waitAfter 30 min.
  10. extractionthe aqueous layer extracted with EtOAc (2×)
  11. washThe combined organics were washed successively with 25% aqueous NH4OAc buffer and brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. customThe residue was purified by column chromatography on silica (EtOAc/hexane 1:1)

Sources & evidence

ORD record
ord-389869ea812746a5b56d2245541ba687
Source dataset
uspto-grants-1998_01
Patent number
US05710170

Reaction notes

Loading…