Triphenylphosphine → 4-{2-[4-(5-Amino-3-tert-butyl-pyrazol-1-yl)-phenoxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 221865Notes

Reaction equation

HRID 221865 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[N:5]=[C:4]([C:14]([CH3:17])([CH3:16])[CH3:15])[CH:3]=1.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([CH2:31][CH2:32]O)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([CH2:31][CH2:32][O:13][C:10]2[CH:11]=[CH:12][C:7]([N:6]3[C:2]([NH2:1])=[CH:3][C:4]([C:14]([CH3:17])([CH3:16])[CH3:15])=[N:5]3)=[CH:8][CH:9]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidineHCID 595579504-(5-Amino-3-tert-butyl-pyrazol-1-yl)phenol

Product 1

HCID 536301924-{2-[4-(5-Amino-3-tert-butyl-pyrazol-1-yl)-phenoxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl esterYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(5-amino-3-tert-butyl-pyrazol-1-yl)-phenol (550 mg, 2.4 mmol) and 4-(2-hydroxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester (505 mg, 2.18 mmol) in 50 mL THF was added ADDP (825 mg, 3.28 mmol) and triphenylphosphine (858 mg, 3.28 mmol). The reaction mixture was stirred at room temperature under nitrogen overnight. The solid was removed by filtration, the filtrate was concentrated and the residue was purified by MPLC (80:20 hexane/EtOAc) to give the desired product 4-{2-[4-(5-amino-3-tert-butyl-pyrazol-1-yl)-phenoxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester 800 mg (83%). 1H-NMR (DMSO-d6) δ 7.40 (d, 2H), 7.00 (d, 2H), 5.35 (s, 1H), 5.0 (s, 2H), 4.0 (m, 2H), 3.90 (m, 2H), 1.70-1.60 (m, 6H), 1.40 (s, 9H), 1.20 (s, 9H), 1.05 (m, 1H); MS LC-MS [M+H]+=443.3, RT=3.10 min.

Workup

  1. customThe solid was removed by filtration
  2. concentrationthe filtrate was concentrated
  3. customthe residue was purified by MPLC (80:20 hexane/EtOAc)

Sources & evidence

ORD record
ord-a7a1b648b2924805ab0481db9bd40987
Source dataset
uspto-grants-2012_06
Patent number
US08207166B2

Reaction notes

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