Lithium Hydroxide → 2-{4-[(Tert-butoxy)carbonyl]piperazin-1-yl}acetic acid

HRID 1601447Notes

Reaction equation

HRID 1601447 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([O:17]CC)=[O:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>O1CCCC1.O.C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([CH2:14][C:15]([OH:17])=[O:16])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 22321826tert-Butyl 4-(2-ethoxy-2-oxoethyl)piperazine-1-carboxylate

Product 1

HCID 27356422-{4-[(Tert-butoxy)carbonyl]piperazin-1-yl}acetic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

Combine 1-t-butoxycarbonyl-4-carboethoxymethylpiperazine (20.8 g, 76.5 mmol) and lithium hydroxide (6.71 g, 160 mmol) in tetrahydrofuran (100 mL) and water (100 mL). After 60 minutes, concentrate in vacuo to give a solid. Combine the solid and water, extract with diethyl ether. Combine the aqueous layer and a 1M aqueous solution of potassium hydrogensulfate (160 mL). Extract three times with chloroform. Evaporate the aqueous layer to give a solid. Triturate the solid repeatedly with warm ethyl acetate and isopropanol and filter. Evaporate each triturate to give solids. Combine the solids obtained by evaporation of the triturates, dissolve in chloroform and evaporate to remove solvent. Dry in vacuo at 50° C. to give 1-t-butoxycarbonyl-4-carboxymethylpiperazine as a solid, mp: 195-197° C. IR (KBr) nmax 3007, 2934, 1691, 1631, 1479, 1453, 1427, 1415, 1393, 1366, 1301, 1283, 1232, 1209, 1177, 1139, 1084 cm-1 ; 1H NMR (CDCl3) ppm 3.71 (br s, 4 H), 3.56 (br s, 2 H), 3.12 (br s, 4 H), 1.46 (s, 9 H); 13C NMR (CDCl3) ppm 169.10, 154.13, 80.70, 58.49, 52.38, 28.25; MS (CI/NH3) m/z 245 (M+1)+.

Workup

  1. concentrationconcentrate in vacuo
  2. customto give a solid
  3. extractionextract with diethyl ether
  4. extractionExtract three times with chloroform
  5. customEvaporate the aqueous layer
  6. customto give a solid
  7. customTriturate the solid repeatedly with warm ethyl acetate and isopropanol
  8. filtrationfilter
  9. customEvaporate
  10. customeach triturate
  11. customto give solids
  12. customCombine the solids obtained by evaporation of the triturates
  13. customevaporate
  14. customto remove solvent
  15. customDry in vacuo at 50° C.

Sources & evidence

ORD record
ord-4d39dde42f044304908d6c6e3229b312
Source dataset
uspto-grants-1999_11
Patent number
US05977139

Reaction notes

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