Hydrochloric Acid → 1-Fmoc-4-Boc-Piperazine-2-acetic acid

HRID 23209

Reaction equation

HRID 23209 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([CH2:14][C:15]([O:17]C)=[O:16])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH-].[Na+].[C:21](Cl)([O:23][CH2:24][CH:25]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]2[C:26]1=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22].Cl>C1COCC1>[C:1]([N:8]1[CH2:13][CH2:12][N:11]([C:21]([O:23][CH2:24][CH:25]2[C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:32]3[C:37]2=[CH:36][CH:35]=[CH:34][CH:33]=3)=[O:22])[CH:10]([CH2:14][C:15]([OH:17])=[O:16])[CH2:9]1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 343679-Fluorenylmethyl chloroformateHCID 2756816Methyl 4-Boc-piperazine-2-acetate

Product 1

HCID 27567961-Fmoc-4-Boc-Piperazine-2-acetic acidYield 91.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A portion (5.2 g; 20 mmol) of the methyl 4-Boc-piperazine-2-acetate product from the previous step was combined with 60 mL of THF and 60 mL of 1 N NaOH (aqueous) and stirred at room temperature for 6 hours to saponify the methyl ester. The reaction was cooled to 0° C., adjusted to pH 9-10 with 10% HCl(aqueous), and 5.2 g (20 mmol) of FMOC-Cl was added. The reaction was stirred at room temperature for 6 hours, (adding 1 N NaOH (aqueous) to maintain pH 9-10) 1 hour, then acidified with 10% HCl to pH=1. The reaction was extracted twice, the combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo to give 8.56 g of the desired 4-Boc-1-Fmoc-piperazine-2-acetic acid (the compound of formula (XXIV)); 1H NMR (CDCl3) δ 1.4 (s,9), 2.5-3.0 (m,5) 3.9-4.2 (m,6), 4.5 (m,1), 7-25 (t,4), 7.32 (t,4), 7.48 (d,4), 7.75 (d, 4).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. additionwas added
  3. stirringThe reaction was stirred at room temperature for 6 hours
  4. extractionThe reaction was extracted twice
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1a9145d13d964fe58e1a408fd6fd08e6
Source dataset
uspto-grants-2005_02
Patent number
US06849739B2

Linked notes

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