Hydrochloric Acid → HCID 53823624, compound

HRID 726756Notes

Reaction equation

HRID 726756 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]([CH:54]4OCC[O:55]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>[CH:10]1([O:15][C:16]2[CH:17]=[C:18]([C@@H:24]([C:48]3[CH:49]=[CH:50][C:51]([CH:54]=[O:55])=[CH:52][CH:53]=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])[CH2:11][CH2:12][CH2:13][CH2:14]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7848Propyl mercaptanHCID 14798Sodium Hydroxide2×HCID 86751959HCID 86751959, compoundHCID 178418339Butyllithium

Product 1

HCID 53823624HCID 53823624, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-Butyllithium (2.4M solution in hexane; 10.6 mL, 25 mmol) was added dropwise to a 0° C. solution of propanethiol (4.6 mL, 51 mmol) in THF (150 mL). After 15 minutes, (1R, 5S)-N-{(3R)-3-(3-cyclopentyloxy-4-methoxyphenyl)-3-[4-(1,3-dioxolan-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 2 (9.7 g, 14.1 mmol) was added as a solid and the reaction mixture was stirred at room temperature for 3 days. The volatiles were then evaporated and the resulting residue was dissolved in EtOH (80 mL) and water (40 mL). Sodium hydroxide (4.5 g, 113 mmol) was added and the mixture heated to reflux for 2 hours. The reaction mixture was cooled to room temperature and treated with HCl 6N to pH 4.5 then heated to reflux for 1 hour. The reaction mixture was cooled to room temperature and treated with NaOH 1N to pH 14 then extracted twice with EtOAc. The organic phase was washed with brine, dried (MgSO4) and evaporated. The residue was purified by flash-chromatography (silica gel, ether) to afford the title compound as a white foam (2.3 g, 41%). 1H NMR (400 MHz, CDCl3): δ 1.55 (m, 2H), 1.75 (m, 6H), 3.30 (m, 2H), 3.80 (s, 3H), 4.20 (t, 1H), 4.60 (m, 1H), 6.60 (s, 1H), 6.65 (d, 1H), 6.75 (d, 1H), 6.90 (d, 2H), 7.35 (d, 2H), 7.75 (d, 2H), 8.40 (d, 2H), 9.95 (s, 1H).

Workup

  1. customThe volatiles were then evaporated
  2. dissolutionthe resulting residue was dissolved in EtOH (80 mL)
  3. temperaturethe mixture heated
  4. temperatureto reflux for 2 hours
  5. temperatureThe reaction mixture was cooled to room temperature
  6. temperaturethen heated
  7. temperatureto reflux for 1 hour
  8. temperatureThe reaction mixture was cooled to room temperature
  9. extractionthen extracted twice with EtOAc
  10. washThe organic phase was washed with brine
  11. dry with materialdried (MgSO4)
  12. customevaporated
  13. customThe residue was purified by flash-chromatography (silica gel, ether)

Sources & evidence

ORD record
ord-0f4675269b6441c495a5db985145db3b
Source dataset
uspto-grants-1998_01
Patent number
US05710170

Reaction notes

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