Triphenylphosphine → 1-Boc-4-[2-(1-methyl-1H-imidazol-2-ylmethoxy)-phenyl]piperazine

HRID 1592763Notes

Reaction equation

HRID 1592763 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[OH:20])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:21][N:22]1[CH:26]=[CH:25][N:24]=[C:23]1[CH2:27]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH2:27][C:23]2[N:22]([CH3:21])[CH:26]=[CH:25][N:24]=2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 573612(1-methyl-1H-imidazol-2-yl)methanolHCID 5462977Diethyl azodicarboxylateHCID 11543684Tert-butyl 4-(2-hydroxyphenyl)piperazine-1-carboxylate

Product 1

HCID 694128371-Boc-4-[2-(1-methyl-1H-imidazol-2-ylmethoxy)-phenyl]piperazineYield 37.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-Boc-4-(2-hydroxy-phenyl)-piperazine (556 mg, 2.0 mmol, 1.0 eq.), (1-methyl-1H-imidazol-2-yl)-methanol (448 mg, 4.0 mmol, 2.0 eq.), triphenylphosphine (1.04 g mg, 4.0 mmol, 2.0 eq.) and THF at 0° C. under nitrogen was added DEAD (0.629 mL, 4.0 mmol, 2.0 eq.) slowly so that temperature of the reaction does not rise above 10° C. After addition was complete, the ice bath was removed and the mixture was stirred at r.t. overnight. Methanol was added, and the mixture was stirred for about 15 minutes and then concentrated. Purification by flash chromatography (35 g SiO2, 40 mL/min, linear gradient 0-8% 2.0 M NH3 in MeOH/CH2Cl2 for 25 minutes and 8% 2.0 M NH3 in MeOH for 7 minutes) afforded the title compound (279 mg, 0.75 mmol, 37%). LRMS (ESI+): 373.3 (M+1).

Workup

  1. customdoes not rise above 10° C
  2. additionAfter addition
  3. customthe ice bath was removed
  4. additionMethanol was added
  5. stirringthe mixture was stirred for about 15 minutes
  6. concentrationconcentrated
  7. customPurification by flash chromatography (35 g SiO2, 40 mL/min, linear gradient 0-8% 2.0 M NH3 in MeOH/CH2Cl2 for 25 minutes and 8% 2.0 M NH3 in MeOH for 7 minutes)

Sources & evidence

ORD record
ord-a8e64d179e40408eb6f73784c4e745ca
Source dataset
uspto-grants-2007_11
Patent number
US07291619B2

Reaction notes

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