Piperidin-4-ol → tert-Butyl 3-(4-hydroxypiperidin-1-yl)azetidine-1-carboxylate

HRID 1922668Notes

Reaction equation

HRID 1922668 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:13][CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([N:17]2[CH2:18][CH2:19][CH:14]([OH:13])[CH2:15][CH2:16]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 79341Piperidin-4-olHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 59605546tert-Butyl 3-(4-hydroxypiperidin-1-yl)azetidine-1-carboxylateYield 23%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A 10 mL round-bottomed flask was charged with a solution of 3-oxoazetidine-1-carboxylic acid tert-butyl ester (1 g, 5.84 mmol), 4-hydroxypiperidine (0.65 g, 6.42 mmol) and 4 Å molecular sieves (10 g) in DCE (50 mL) The reaction mixture was stirred for 4 h at room temperature. Sodium triacetoxyborohydride (2.48 g, 11.68 mmol) was added and the reaction mixture was stirred for 18 h at room temperature. The suspension was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, EtOAc:cyclohexane, gradient 0:100 to 100:0) to give 3-(4-Hydroxypiperidin-1-yl)azetidine-1-carboxylic acid tert-butyl ester as a colourless oil (0.34 g, 23%). 1H NMR (CDCl3, 400 MHz) δ 3.92 (t, J=7.8 Hz, 2H); 3.87-3.72 (m, 3H);(m, 1H); 2.68-2.63 (m, 2H); 2.09-2.03 (m, 2H); 1.96-1.91 (m, 2H); 1.69-1.55 (m, 2H); 1.43 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred for 18 h at room temperature
  2. filtrationThe suspension was filtered through Celite
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by flash chromatography (Si—PPC, EtOAc:cyclohexane, gradient 0:100 to 100:0)

Sources & evidence

ORD record
ord-c4be1c3fdc8e4d82b0f92bb8d0a976b5
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

Loading…