Hydrochloric Acid → N-[(R)-1-[3-(4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-beta-alanine

HRID 1934388Notes

Reaction equation

HRID 1934388 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11](/[CH:14]=[CH:15]/[C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([NH:26][C@H:27]([C:32]#[CH:33])[CH2:28][C:29]([OH:31])=[O:30])=[O:25])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>C(OCC)(=O)C>[NH:8]1[CH2:9][CH2:10][CH:11](/[CH:14]=[CH:15]/[C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([NH:26][C@H:27]([C:32]#[CH:33])[CH2:28][C:29]([OH:31])=[O:30])=[O:25])[CH2:19]2)=[O:17])[CH2:12][CH2:13]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86758027N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-beta-alanine

Product 1

HCID 86758029N-[(R)-1-[3-(4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-beta-alanineYield 72.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-β-alanine (1.23 g) in ethyl acetate (12 ml) was added 4N HCl in ethyl acetate (6.66 ml) at room temperature, and the reaction mixture was stirred for 2 hours. The precipitates were filtered, washed with diethyl ether and purified by preparative HPLC eluting with 0.1% trifluoroacetic acid-CH3CN (9:1), then the fractions containing the object compound were concentrated in vacuo. The residue was resolved in water, neutralized with 1N aq. NaOH, desalted by using the resin of HP-20 eluting with isopropanol-H2O (1:1), freeze-dried to give N-[(R)-1-[3-(4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-β-alanine as a white powder (0.7 g).

Workup

  1. filtrationThe precipitates were filtered
  2. washwashed with diethyl ether
  3. custompurified by preparative HPLC
  4. washeluting with 0.1% trifluoroacetic acid-CH3CN (9:1)
  5. additionthe fractions containing the object compound
  6. concentrationwere concentrated in vacuo
  7. washeluting with isopropanol-H2O (1:1)
  8. customfreeze-dried

Sources & evidence

ORD record
ord-27029d51c3f94dfcb9013ba164b189e4
Source dataset
uspto-grants-2002_05
Patent number
US06384028B1

Reaction notes

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