Triethylamine → 4-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1022857Notes

Reaction equation

HRID 1022857 reaction equation
N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:32][C:33]1[C:42]([OH:43])=[CH:41][CH:40]=[C:39]2[C:34]=1[CH:35]=[CH:36][N:37]=[CH:38]2.[C:44]([N:51]1[CH2:56][CH2:55][CH:54](O)[CH2:53][CH2:52]1)([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45].C(N(CC)CC)C>ClCCl>[C:47]([O:46][C:44]([N:51]1[CH2:56][CH2:55][CH:54]([O:43][C:42]2[C:33]([Br:32])=[C:34]3[C:39](=[CH:40][CH:41]=2)[CH:38]=[N:37][CH:36]=[CH:35]3)[CH2:53][CH2:52]1)=[O:45])([CH3:50])([CH3:48])[CH3:49]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 1360928955-Bromo-6-isoquinolinol

Product 1

HCID 576469744-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3.75 mL (4.15 g, 23.8 mmol) of diethyl azo dicarboxylate were added to 12.7 g (19.9 mmol) of polymer-bound triphenylphosphine (PS—PPh3, approx. 1.6 mmol/g, Argonaut) in 250 mL of dichloromethane at 0° C. and stirred for 15 min. 4.45 g (19.9 mmol) 5-bromo isoquinoline-6-ol (9), 4.0 g (19.9 mmol) Boc-(4-hydroxy)piperidine and 4.1 mL (3.0 g, 29.8 mmol) triethyl amine were added. The mixture was shaken for 16 h. The polymer was removed by filtration through Celite and the solvents were distilled off. 20 mL dichloromethane were added and the precipitate was isolated by filtration. The crude product (8 g) was purified by flash chromatography using ethyl acetate/n-heptane as eluent to give 4.78 g (60%) of compound 11.

Workup

  1. stirringThe mixture was shaken for 16 h
  2. customThe polymer was removed by filtration through Celite
  3. distillationthe solvents were distilled off
  4. addition20 mL dichloromethane were added
  5. customthe precipitate was isolated by filtration
  6. customThe crude product (8 g) was purified by flash chromatography

Sources & evidence

ORD record
ord-3779663aedd041a3aadfae89adc2f6b6
Source dataset
uspto-grants-2014_05
Patent number
US08722671B2

Reaction notes

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