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

HRID 1780340노트

반응식

HRID 1780340 반응식
[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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-e4f419877059465a8f073a60bde67a31
출처 데이터셋
uspto-grants-1997_05
특허 번호
US05629325

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