Hydrochloric Acid → HCID 57252838, compound

HRID 726759Notes

Reaction equation

HRID 726759 reaction equation
[CH2:1]([Li])[CH2:2]CC.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]([CH2:54][CH:55]4[O:59][CH2:58][CH2:57][O:56]4)=[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.[OH-].[Na+].Cl>C1COCC1>[CH2:1]([O:59][CH:55]([O:56][CH2:57][CH3:58])[CH2:54][C:51]1[CH:52]=[CH:53][C:48]([C@H:24]([C:18]2[CH:19]=[CH:20][C:21]([O:22][CH3:23])=[C:16]([O:15][CH:10]3[CH2:14][CH2:13][CH2:12][CH2:11]3)[CH:17]=2)[CH2:25][C:42]2[CH:47]=[CH:46][N:45]=[CH:44][CH:43]=2)=[CH:49][CH:50]=1)[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7848Propyl mercaptanHCID 14798Sodium Hydroxide2×HCID 131720397HCID 131720397, compoundHCID 178418339Butyllithium

Product 1

HCID 57252838HCID 57252838, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-Butyllithium (2.4M solution in hexane; 13.2 mL, 31.3 mmol) was added dropwise to a solution of 1-propanethiol (3.47 mL, 38.3 mmol) in THF (160 mL) at 0° C. After 30 min, (1R,5S)-N-{(3R)-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-[4-(1,3-dioxolan-2-ylmethyl)phenyl]-2-(4-pyridyl)propanoyl}-10,10-dimethyl-3-thia-4-azatricyclo[5.2.1.01,5 ]decane-3,3-dioxide from Step 3 (12.2 g, 17.4 mmol) was added as a solid and the reaction mixture was stirred at room temperature for 2.5 h. The volatiles were then evaporated and the resulting residue was dissolved in EtOH (100 mL) and water (50 mL). Sodium hydroxide (5.57 g, 139 mmol) was added and the mixture heated to reflux for 2.5 h. The reaction mixture was cooled to room temperature and treated with 6N HCl to pH 4.5 then heated to reflux for 2 h. The reaction mixture was cooled to room temperature and treated with 1N NaOH to pH 14, then extracted with EtOAc (3×). The combined organics were washed successively with 25% aqueous NH4OAc buffer, water and brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography on silica (acetone/ether 1:9→1:4→1:3) to afford the title compound as an off-white gum (1.17 g, 14%).

Workup

  1. customThe volatiles were then evaporated
  2. dissolutionthe resulting residue was dissolved in EtOH (100 mL)
  3. temperaturethe mixture heated
  4. temperatureto reflux for 2.5 h
  5. temperatureThe reaction mixture was cooled to room temperature
  6. temperaturethen heated
  7. temperatureto reflux for 2 h
  8. temperatureThe reaction mixture was cooled to room temperature
  9. extractionextracted with EtOAc (3×)
  10. washThe combined organics were washed successively with 25% aqueous NH4OAc buffer, water and brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customThe residue was purified by column chromatography on silica (acetone/ether 1:9→1:4→1:3)

Sources & evidence

ORD record
ord-ad0e0e4d44f84ba89e9a7747b04c3467
Source dataset
uspto-grants-1998_01
Patent number
US05710170

Reaction notes

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