Trifluoroacetic acid → 5-Phenyl-6-chloro-3-(2-(S)-azetidinylmethoxy)pyridine hydrochloride

HRID 1780340Notes

Reaction equation

HRID 1780340 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([O:14][CH2:15][C@@H:16]3[CH2:19][CH2:18][N:17]3C(OC(C)(C)C)=O)[CH:10]=[N:11][C:12]=2[Cl:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[ClH:13].[C:1]1([C:7]2[CH:8]=[C:9]([O:14][CH2:15][C@@H:16]3[CH2:19][CH2:18][NH:17]3)[CH:10]=[N:11][C:12]=2[Cl:13])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 228726875-Phenyl-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine

Product 1

HCID 98397015-Phenyl-6-chloro-3-(2-(S)-azetidinylmethoxy)pyridine hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 5-phenyl-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 67a (380 mg) was added TFA in methylene chloride at 0° C., and the mixture was stirred for 30 minutes. The volatiles were then removed under vacuum. The residue was neutralized with NaHCO3 to pH 8, then extracted with methylene chloride, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with methylene chloride:methanol:NH4OH 10:1:0.1 to afford to give the free base of the title compound. MS (CI/NH3) m/z 275 (M+H)+, 277 (M+2H)+. 1H NMR (CDCl3, 300 MHz) δ2.21-2.46 (m, 2H), 3.41-3.50 (m, 1H), 3.73 (dd, J=7.5, 8.0 Hz, 1H), 4.0-4.12 (m, 2H), 4.25-4.35 (m, 1H), 7.26 (d, J=3 Hz, 1H), 7.41-7.48 (m, 5H), 8.09 (d, J=3 Hz, 1H). The base was converted to the salt by treatment with hydrogen chloride saturated ethanol to give the title compound (256 mg). mp 148°-150° C. MS (DCI/NH3) m/z 275 (M+H)+. 1H NMR (D2O, 300 MHz) δ: 2.66-274 (m, 2H), 4.06-4.21 (m, 3H), 4.46 (d, J=4.1, 2H), 4.92-5.01 (m, 1H), 7.50-7.59 (m, 5H), 7.60 (d, J=3.0, 1H), 8.20 (d, J=3.0, 1H).

Workup

  1. customThe volatiles were then removed under vacuum
  2. extractionextracted with methylene chloride, which
  3. dry with materialwas dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was chromatographed on a silica gel column
  6. washeluting with methylene chloride:methanol:NH4OH 10:1:0.1
  7. customto afford

Sources & evidence

ORD record
ord-e4f419877059465a8f073a60bde67a31
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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