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

HRID 1247160Notes

Reaction equation

HRID 1247160 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-0b2dd444d9d34ef5a1e227e9b2e7472b
Source dataset
uspto-grants-2006_10
Patent number
US07129245B2

Reaction notes

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