Iodine → HCID 24904639, compound

HRID 2167501Notes

Reaction equation

HRID 2167501 reaction equation
[NH:1]1[CH2:5][CH2:4][CH:3]([OH:6])[CH2:2]1.[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[CH:12]=O.II.[BH4-].[Na+]>CO.O1CCCC1.O>[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[CH2:12][N:1]1[CH2:5][CH2:4][CH:3]([OH:6])[CH2:2]1

Participants

8

Reactant 4

HCID 807IodineHCID 115693-MethoxybenzaldehydeHCID 982104-HydroxypyrrolidineHCID 4311764Sodium borohydride

Product 1

HCID 24904639HCID 24904639, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To pyrrolidin-3-ol (3.4 g, 39 mmol) in methanol (150 mL) was added 3-methoxybenzaldehyde (6.4 g, 47 mmol) and iodine (0.40 g, 32 mmol). After stirring for 5 h, the reaction mixture was cooled to 0° C. and sodium borohydride (2.9 g, 78 mmol) was added portionwise. The reaction mixture was warmed to ambient temperature and stirred overnight. Water (10 mL) was added and most of the tetrahydrofuran was removed in vacuo. Additional water (25 mL) was added and the aqueous layer was extracted with methylene chloride (50 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (methylene chloride to 90:9:1 methylene chloride/methanol/ammonium hydroxide) to provide 1-(3-methoxybenzyl)pyrrolidin-3-ol (2.0 g, 25%) as a yellow oil: 1H NMR (DMSO-d6, 300 MHz) δ 7.21 (dd, J=8.1, 8.1 Hz, 1H), 6.87-6.77 (m, 3H), 4.66 (d, J=4.5 Hz, 1H), 4.21-4.14 (m, 1H), 3.73 (s, 3H), 3.56-3.45 (m, 2H), 2.64 (dd, J=9.6, 6.3 Hz, 1H), 2.58-2.49 (m, 1H), 2.43-2.34 (m, 1H), 2.28 (dd, J=9.6, 7.5 Hz, 1H), 2.04-1.92 (m, 1H), 1.57-1.51 (m, 1H).

Workup

  1. temperatureThe reaction mixture was warmed to ambient temperature
  2. stirringstirred overnight
  3. customwas removed in vacuo
  4. additionAdditional water (25 mL) was added
  5. extractionthe aqueous layer was extracted with methylene chloride (50 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (methylene chloride to 90:9:1 methylene chloride/methanol/ammonium hydroxide)

Sources & evidence

ORD record
ord-b5f484edd6c34f7d9557f17d1975636f
Source dataset
uspto-grants-2015_06
Patent number
US09045468B2

Reaction notes

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