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

HRID 365840Notes

Reaction equation

HRID 365840 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@@H:11]2[CH2:14][CH2:13][N:12]2C(OC(C)(C)C)=O)[CH:5]=[N:6][C:7]=1[Cl:8].C(O)(C(F)(F)F)=O>C(Cl)Cl>[ClH:8].[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@@H:11]2[CH2:14][CH2:13][NH:12]2)[CH:5]=[N:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 228726673-(1-BOC-2-(S)-azetidinylmethoxy)-5-bromo-6-chloropyridine

Product 1

HCID 228726695-Bromo-6-chloro-3-(2-(S)-azetidinylmethoxy)pyridine hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 5-bromo-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 66a (360 mg, 0.95 mmol) was added TFA in CH2Cl2 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 CH2Cl2, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with CH2Cl2 :MeOH:NH4OH 10:1:0.1 to afford to give the free base of the title compound. The base was converted to the salt by treatment with hydrogen chloride saturated EtOH to give the title compound (224 mg). mp 168-169° C. MS (CI/NH3) m/z 277/279 (M+H)+. 1H NMR (D2O, 300 MHz) δ2.69 (dd, J=7.0, 8.5, 2H), 4.06-4.20 (m, 3H), 4.43 (d, J=4.5, 2H), 4.91-4.99 (m, 1H), 7.94 (d, J=3.0, 1H), 8.17 (d, J=3.0, 1H). Anal. Calcd for C9H10N2OBrCl·0.9 HCl: C, 34.83; H, 3.54; N, 9.03. Found: C, 34.85; H, 3.56; N, 8.82. [α:]25D=-4.81° (c 0.13, MeOH).

Workup

  1. customThe volatiles were then removed under vacuum
  2. extractionextracted with CH2Cl2, which
  3. dry with materialwas dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was chromatographed on a silica gel column
  6. washeluting with CH2Cl2 :MeOH:NH4OH 10:1:0.1
  7. customto afford

Sources & evidence

ORD record
ord-7ab891ffc9c54a439e661acff308cd40
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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