Formaldehyde → Tert-butyl 4-(3-hydroxyprop-1-yn-1-yl)piperidine-1-carboxylate

HRID 1063370Notes

Reaction equation

HRID 1063370 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]=[C:15](Br)Br)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[CH2:23]=[O:24]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][CH2:23][OH:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 11474132Tert-butyl 4-(2,2-dibromovinyl)piperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 69786345Tert-butyl 4-(3-hydroxyprop-1-yn-1-yl)piperidine-1-carboxylateYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6.0 g (16.3 mmol) of 4-(2,2-Dibromo-vinyl)-piperidine-1-carboxylic acid tert-butyl ester in 150 ml THF was treated at −78° C. with 21.4 ml (34.2 mmol) of n-BuLi (ca 1.6 M in hexane). After 2 h at this temperature 4.9 g (16.3 mmol) of paraformaldehyde were added. The reaction was warmed up to RT for 3 h and after 1 h at this temperature partitioned between water/ether (3×). The organic phases were washed with aqueous 10% NaCl, dried over Na2SO4 and evaporated. Purification by flash-chromatography on silica gel (hexane/EtOAc 4:1) gave 3.34 g (86%) of 4-(3-Hydroxy-prop-1-ynyl)-piperidine-1-carboxylic acid tert-butyl ester, MS: 239 (M).

Workup

  1. custompartitioned between water/ether (3×)
  2. washThe organic phases were washed with aqueous 10% NaCl
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. customPurification by flash-chromatography on silica gel (hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-02f7d00b87ec4b98abdc6aa25332ee64
Source dataset
uspto-grants-2005_11
Patent number
US06964974B2

Reaction notes

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