Tetrahydrofuran → 1-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine

HRID 988713Notes

Reaction equation

HRID 988713 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Mg]Br.[Cl-].[NH4+].C1C[O:24][CH2:23]C1>>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([CH2:14][CH2:23][OH:24])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 178418573HCID 178418573, compound2×

Product 1

HCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidineYield 31%

Procedure

A solution of 1-(tert-butoxycarbonyl)piperidine-4-carboxaldehyde (14.9 g, 69.8 mmol) in THF at −78° C. was treated with methylmagnesium bromide (25.6 mL, 3.0 M in THF, 76.8 mmol). After 16 h, the mixture was treated with additional methylmagnesium bromide (15.0 mL, 3.0 M in THF). After 1 h, the mixture was treated with saturated aqueous ammonium chloride and partitioned between EtOAc and water. The aqueous phase was washed with EtOAc, the organic extracts were combined and washed with brine, dried (MgSO4), and concentrated. The residue was purified by column chromatography (SiO2: 30 to 40% EtOAc:hexanes) affording 5.0 g (31%) of the title compound.

Workup

  1. waitAfter 1 h
  2. custompartitioned between EtOAc and water
  3. washThe aqueous phase was washed with EtOAc
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (SiO2: 30 to 40% EtOAc:hexanes)

Sources & evidence

ORD record
ord-de7d8e9b91e84998ab666f65d3126938
Source dataset
uspto-grants-2003_10
Patent number
US06635657B1

Reaction notes

Loading…