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

HRID 1760424Notes

Reaction equation

HRID 1760424 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+].Cl.[C:22](Cl)([O:24][CH2:25][CH:26]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]2[C:27]1=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23]>C1COCC1>[C:1]([N:8]1[CH2:13][CH2:12][N:11]([C:22]([O:24][CH2:25][CH:26]2[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:33]3[C:38]2=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:23])[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 Acid2×HCID 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-c5d8042b5e7d444dbd285881fe465f61
Source dataset
uspto-grants-2005_01
Patent number
US06841674B2

Reaction notes

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