Triphenylphosphine → 3-(1-Amino-isoquinolin-6-yloxy)piperidin-1--carboxylic acid tert-butyl ester

HRID 1435963Notes

Reaction equation

HRID 1435963 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:34][C:35]1[C:44]2[C:39](=[CH:40][C:41](O)=[CH:42][CH:43]=2)[CH:38]=[CH:37][N:36]=1.CCOC(/N=N/C(OCC)=O)=O.[OH-].[Na+]>C1COCC1.CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([O:14][C:41]2[CH:40]=[C:39]3[C:44](=[CH:43][CH:42]=2)[C:35]([NH2:34])=[N:36][CH:37]=[CH:38]3)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 1514398(R)-1-Boc-3-hydroxypiperidineHCID 5462977Diethyl azodicarboxylateHCID 1357539911-Aminoisoquinolin-6-ol

Product 1

HCID 775634643-(1-Amino-isoquinolin-6-yloxy)piperidin-1--carboxylic acid tert-butyl esterYield 20.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (209 mg, 1.04 mmol), triphenylphosphine (327 mg, 1.249 mmol), 1-amino-isoquinolin-6-ol (200 mg, 1.249 mmol) in THF (4 ml) and DMF (394 μL) at 0° C., under argon, was added dropwise diethylazodicarboxylate (197 mL) over 5 min. The mixture was then warmed to ambient temperature and stirred for 48 h. Water was then added and the mixture basified with dilute NaOH. The mixture was extracted with ethyl acetate (X3), dried (sodium sulphate) filtered and evaporated under reduced pressure to give a residue. Flash chromatography of the residue on silica (eluent: 2-10% methanol in dichloromethane with 1% aqueous ammonia) gave (S) 3-(1-amino-isoquinolin-6-yloxy)piperidin-1--carboxylic acid tert-butyl ester (72 mg), El-MS: m/z=344.1 [M+H]+.

Workup

  1. extractionThe mixture was extracted with ethyl acetate (X3)
  2. dry with materialdried (sodium sulphate)
  3. filtrationfiltered
  4. customevaporated under reduced pressure
  5. customto give a residue

Sources & evidence

ORD record
ord-09d2470d721847ecba85d1d9cbd6ed5f
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

Loading…