Isopropyl chloroformate → Isopropyl 4-Hydroxypiperidine-1-carboxylate

HRID 1811594Notes

Reaction equation

HRID 1811594 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(N(CC)C(C)C)(C)C.Cl[C:18]([O:20][CH:21]([CH3:23])[CH3:22])=[O:19]>ClCCl>[CH:21]([O:20][C:18]([N:5]1[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]1)=[O:19])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 7917Isopropyl chloroformateHCID 79341Piperidin-4-olHCID 81531Diisopropylethylamine

Product 1

HCID 16745126Isopropyl 4-Hydroxypiperidine-1-carboxylateYield 83.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
12.5 °C

Procedure

A magnetically stirred solution of 4-hydroxypiperidine (70.3 g, 695 mmol) and N,N-diisopropylethylamine (105 mL, 600 mmol) in dichloromethane (1.0 L) was cooled to 10° C. under N2. A solution of isopropyl chloroformate (1.0 M in toluene, 580 mL, 580 mmol) was added dropwise over 2 h, maintaining a temperature of 10-15° C. The reaction mixture was stirred for an additional 2 h and then extracted with 1 N HCl (1.2 L). The organic extract was dried over MgSO4, and the solvent was removed under reduced pressure to give the title compound (90.3 g, 83%) as a pale, straw-colored oil. Exact Mass calculated for C9H17NO3: 187.1. Found: LCMS m/z=188.2 (M+H+), 210.3 (M+Na+); 1H NMR (400 MHz, CDCl3) δ 1.24 (d, J=6.3 Hz, 6H), 1.47 (m, 2H), 1.86 (m, 2H), 3.08 (m, 2H), 3.86 (m, 3H), 4.90 (m, 1H).

Workup

  1. extractionextracted with 1 N HCl (1.2 L)
  2. extractionThe organic extract
  3. dry with materialwas dried over MgSO4
  4. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-c72f0aa2c46749f19b793f383b6c1fb7
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

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