Acetic Acid → 1-Benzyl 4-tert-butyl (2R)-2-(hydroxymethyl)piperazine-1,4-dicarboxylate

HRID 902056Notes

Reaction equation

HRID 902056 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][C@H:12]1[C:24](O)=[O:25])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.C(O)(=O)C>O1CCCC1.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:13][C@@H:12]1[CH2:24][OH:25])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 6331BoraneHCID 1512536(S)-1-((Benzyloxy)carbonyl)-4-(tert-butoxycarbonyl)piperazine-2-carboxylic acid

Product 1

HCID 272817631-Benzyl 4-tert-butyl (2R)-2-(hydroxymethyl)piperazine-1,4-dicarboxylateYield 78.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To (S)-1-(benzyloxycarbonyl)4-(tert-butyloxycarbonyl)-piperazine-2-carboxylic acid (15.2 g, 0.04 mol) in tetrahydrofuran (200 ml) at 0° C. under argon was added borane (1M soln. in THF; 111 ml, 0.11 mol) dropwise over 15 min. The resulting mixture was stirred for 1 h, maintaining the temperature between 0° C. and 5° C., and then allowed to reach room temperature and stirred a further 18 h. The mixture was then carefully added, with stirring, to 5% g. acetic acid in water (1 l). After 1 h, the organics were evaporated in vacuo and the residual aqueous extracted with ethyl acetate (300 ml×4). The combined extracts were dried (Na2SO4), and evaporated in vacuo to a colourless oil. Chromatography on silica gel eluting with ethyl acetate-hexane mixtures afforded the title product (11 g, 75%) as a colourless oil.

Workup

  1. temperaturemaintaining the temperature between 0° C. and 5° C.
  2. customto reach room temperature
  3. stirringstirred a further 18 h
  4. additionThe mixture was then carefully added
  5. stirringwith stirring, to 5% g
  6. waitAfter 1 h
  7. customthe organics were evaporated in vacuo
  8. extractionthe residual aqueous extracted with ethyl acetate (300 ml×4)
  9. dry with materialThe combined extracts were dried (Na2SO4)
  10. customevaporated in vacuo to a colourless oil

Sources & evidence

ORD record
ord-2b6a3aa82b5b4c9ca34a76720571c0fe
Source dataset
uspto-grants-2008_04
Patent number
US07365077B2

Reaction notes

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