Ether hydrochloride → HCID 68612172, compound

HRID 2095385Notes

Reaction equation

HRID 2095385 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:18]=[N:19][CH:20]=[C:21]([O:23][CH2:24][C@@H:25]3[CH2:29][CH2:28][CH2:27][N:26]3C(OC(C)(C)C)=O)[CH:22]=2)[CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:37].CCOCC>CO>[ClH:37].[CH2:1]([O:8][CH2:9][CH2:10][CH:11]1[CH2:12][CH2:13][N:14]([C:17]2[CH:18]=[N:19][CH:20]=[C:21]([O:23][CH2:24][C@@H:25]3[CH2:29][CH2:28][CH2:27][NH:26]3)[CH:22]=2)[CH2:15][CH2:16]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 10953452Ether hydrochlorideHCID 59371508HCID 59371508, compound

Product 1

HCID 68612172HCID 68612172, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-[4-[2-(benzyloxy)ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (120 mg, 0.24 mmol) in MeOH (0.5 mL) was added 2N anhydrous HCl/ether (2 mL) under Ar at room temperature. The mixture was stirred at room temperature overnight. After the solvent was evaporated, the residue was dissolved in deionized water. The aqueous solution was washed three times with EtOAc, then filtered over a cotton plug. The water was removed under reduced pressure at 35° C., and the residue was purified by preparative HPLC (ACE AQ 150×21.2 mm; UV detection at 254 and 280 nm; flow 10.0 mL/min; gradient of 0 to 50% CH3CN in water [both containing 0.05 vol % CF3COOH] in 25 min, to 100% in another 5 min; tR 12.8-19.4 min) to obtain, after evaporation, the trifluoroacetate (131 mg). This salt was treated with PL-HCO3 MP anion exchange resin (Polymer Laboratories) in MeOH to afford the free amine, which was dissolved in MeOH (0.5 mL) and treated again with 2N anhydrous HCl/ether (2 mL) under Ar protection at room temperature. The mixture was stirred at room temperature overnight. After the solvent was evaporated, the residue was dissolved in deionized water (approx. 25 mL). The solution was filtered over a cotton plug, and the water was removed under reduced pressure at 35° C. After lyophilization from water, the hydrochloride (103 mg) was obtained as a yellow glass. [α]20D+1.8 (c 0.555 g/L, MeOH). 1H NMR (D2O, 400 MHz) δ 7.89 (s, 1H), 6.67 (s, 1H), 7.32 (s, 1H), 7.26-7.18 (m, 5H), 4.49 (m, 3H), 4.37 (m, 1H), 4.17 (m, 1H), 3.63 (m, 2H), 3.44 (t, 2H, J=6.8 Hz), 3.27 (t, 2H, J=6.8 Hz), 2.82 (m, 2H), 2.16-2.13 (m, 1H), 2.02-1.93 (m, 2H), 1.90-1.79 (m, 1H), 1.60 (m, 2H), 1.42 (m, 1H), 1.38 (m, 2H), 1.11 (m, 2H). 13C NMR (D2O, 100 MHz) δ 156.4, 148.8, 137.0, 128.2, 128.0, 127.7, 121.8, 117.3, 114.3, 72.0, 67.2, 58.1, 47.5, 45.6, 34.5, 31.2, 30.0, 25.4, 23.0. HRMS (ESI) calcd for C24H34N3O2 (M+H+) m/z 396.2651, found 396.2637. Anal. Calcd. for C24H33N3O2.3.0HCl.0.85H2O: C, 55.41; H, 7.30; N, 8.08; Cl, 20.44. Found: C, 55.64; H, 7.57; N, 8.21; Cl, 20.43.

Workup

  1. customAfter the solvent was evaporated
  2. dissolutionthe residue was dissolved in deionized water
  3. washThe aqueous solution was washed three times with EtOAc
  4. filtrationfiltered over a cotton plug
  5. customThe water was removed under reduced pressure at 35° C.
  6. customthe residue was purified by preparative HPLC (ACE AQ 150×21.2 mm
  7. waitgradient of 0 to 50% CH3CN in water [both containing 0.05 vol % CF3COOH] in 25 min
  8. waitto 100% in another 5 min
  9. customtR 12.8-19.4 min) to obtain
  10. customafter evaporation
  11. additionThis salt was treated with PL-HCO3 MP anion exchange resin (Polymer Laboratories) in MeOH

Sources & evidence

ORD record
ord-f3161f78f4584e75933efed8b35b850f
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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