Potassium Carbonate → 3-(1-Boc-2-(s)-pyrrolidinylmethoxy)-6-chloro-5-methylpyridine

HRID 365912Notes

Reaction equation

HRID 365912 reaction equation
[C:1]([O:4][C:5]1[CH:6]=[C:7]([CH3:12])[C:8]([Cl:11])=[N:9][CH:10]=1)(=O)[CH3:2].C(=O)([O-])[O-].[K+].[K+].[C:19](C1(C)C=CC=C[C@]1(C)S([O-])(=O)=O)([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].[NH:38]1C[CH2:41][CH2:40][CH2:39]1>CO>[C:19]([N:38]1[CH2:39][CH2:40][CH2:41][C@H:2]1[CH2:1][O:4][C:5]1[CH:10]=[N:9][C:8]([Cl:11])=[C:7]([CH3:12])[CH:6]=1)([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 218288696-Chloro-5-methylpyridin-3-yl acetateHCID 1317220211-BOC-2-(S)-methyltoluenesulfonate pyrrolidine

Product 1

HCID 229618403-(1-Boc-2-(s)-pyrrolidinylmethoxy)-6-chloro-5-methylpyridineYield 46.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 5-acetoxy-2-chloro-3-methylpyridine (1.80 g, 8.9 mmol) in MeOH (5 mL) was added potassium carbonate (1.4 g, 10.1 mmol). The reaction mixture was allowed to stir at room tenperature for 2.5 h. Solvent was evaporated. The residue was then dissolved in DMF, and 1-BOC-2-(S)-methyltoluenesulfonate-pyrrolidine (2.0 g, 5.63 mmol) from a above was added. The reaction mixture was stirred at 60° C. for 16 h. Solvent was evaporated. The residue was chromatographed (silica gel; hexane/EtOAc, 10:1 to 3:1) to afford an oil (850 mg, 30%): 1H NMR δ 1.47 (s, 9H), 1.80-2.00 (m, 2H), 2.00-2.08 (m, 2H), 2.34 (s, 3H), 3.24-3.44 (m, 2H), 3.92 (m, 1H), 4.02-4.20 (m, 2H), 7.16 (m, 1H), 7.92 (d, 1H, J=2.5 Hz); MS (CI/NH3) m/z 227 (M+H)+.

Workup

  1. customSolvent was evaporated
  2. dissolutionThe residue was then dissolved in DMF
  3. stirringThe reaction mixture was stirred at 60° C. for 16 h
  4. customSolvent was evaporated
  5. customThe residue was chromatographed (silica gel; hexane/EtOAc, 10:1 to 3:1)

Sources & evidence

ORD record
ord-63fd7c10c4ba43279e2579e8e88b92b3
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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