Methyl iodide → Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-methoxypyrrolidin-1-carboxylate

HRID 575978Notes

Reaction equation

HRID 575978 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([Cl:21])[CH:15]=2)([OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:25]>O1CCCC1>[Cl:21][C:16]1[CH:15]=[C:14]([C:10]2([O:13][CH3:25])[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]2)[CH:19]=[C:18]([F:20])[CH:17]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67402932Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 67402360Tert-butyl 3-(3-chloro-5-fluorophenyl)-3-methoxypyrrolidin-1-carboxylateYield 71.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Preparation according to Preparation 2. Tert-butyl-3-(3-chloro-5-fluorophenyl)-3-hydroxypyrrolidin-1-carboxylate (2.1 g, 6.67 mmol) in dry tetrahydrofuran (50 mL), sodium hydride (60% dispersion in mineral oil, 0.40 g, 10 mmol), iodomethane (0.83 mL, 13.3 mmol). Purification by flash column chromatography on silica gel (ethyl acetate/isooctane, 1:9 to 1:1) gave the title compound (1.57 g, 71%). MS m/z (rel. intensity, 70 eV) 275 (33), 273 (bp), 256 (42), 228 (32), 57 (77).

Workup

  1. customPreparation
  2. customaccording to Preparation 2
  3. customPurification by flash column chromatography on silica gel (ethyl acetate/isooctane, 1:9 to 1:1)

Sources & evidence

ORD record
ord-56ebb72d106c483bafbdf3b6191dd288
Source dataset
uspto-grants-2015_05
Patent number
US09035073B2

Reaction notes

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