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N-Boc-3-mesyloxypiperidine → 3-(1-Chloroisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester

HRID 1435990
Notes
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Reaction equation

HRID 1435990 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:12])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][CH:22](OS(C)(=O)=O)[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].CCN(P1(N(C)CCCN1)=NC(C)(C)C)CC>C(#N)C>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][CH:22]([O:12][C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[C:2]([Cl:1])=[N:3][CH:4]=[CH:5]3)[CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 568122N-Boc-3-mesyloxypiperidineHCID 199900182-tert-butylimino-N,N-diethyl-1-methyl-1,3,2lambda5-diazaphosphinan-2-amineHCID 1357421771-chloro-2H-isoquinolin-6-one

Product 1

HCID 866129773-(1-Chloroisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl esterYield 29.2%

Reagents, catalysts & solvents 1

HCID 6342
Acetonitrile
Solvent

Conditions

Temperature
120 °C

Procedure

The 1-chloro-6-methoxyisoquinoline was prepared as described in WO 00/24718 (Akzo Nobel N.V.). Alternatively it can be prepared from 3-methoxybenzaldehyde using the same procedure as in Example 15A (for the synthesis of 1-chloro-6-methoxy-7-methyl-isoquinoline). The 1-chloro-6-methoxyisoquinoline is demethylated according to the procedure described in WO 00/24718 to afford 1-chloro-6-hydroxyisoquinoline. A suspension of 1-chloro-6-hydroxyisoquinoline (0.18 g, 1 mmol), 3-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (336 mg, 1.2 mmol) and 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine on polystyrene (500 mg, ˜2.2mmol/g loading) in acetonitrile (4 ml) were heated at 120° C. over a period of 900 seconds using the microwave. The excess supported reagent was removed by filtration, washing with methanol, and the filtrate evaporated to dryness under reduced pressure. Since the reaction had not gone to completion, the above procedure was repeated. Purification of the crude material was achieved by chromatography on silica (eluent: 0-25% ethyl acetate in heptane) to afford 3-(1-chloroisoquinolin-6-yloxy)piperidine-1-carboxylic acid tert-butyl ester (106 mg), El-MS: m/z=363.7 [M+H]+.

Workup

  1. customwas removed by filtration
  2. washwashing with methanol
  3. customthe filtrate evaporated to dryness under reduced pressure
  4. customPurification of the crude material

Sources & evidence

ORD record
ord-04dfb89f95bf471b8ebd5aef018a60bc
Source dataset
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07618985B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes