Ammonia → (s)-1-n-boc-pipecolamide

HRID 851733Notes

Reaction equation

HRID 851733 reaction equation
[N:1]1([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][CH2:8][CH2:7][CH2:6][C@H:2]1[C:3](O)=[O:4].C([N:19](CC)CC)C.ClC(OCC(C)C)=O.N>C(OCC)(=O)C>[N:1]1([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([NH2:19])=[O:4]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 688617(2S)-1-((tert-butoxy)carbonyl)piperidine-2-carboxylic acid

Product 1

HCID 2756821(s)-1-n-boc-pipecolamideYield 78%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

2.29 g (10 mmoles) of BOC-HPro-OH are dissolved in 30 ml of ethyl acetate, 1.4 ml (10 mmoles) of triethylamine are added to the solution, the mixture is cooled to -10° C., and then 1.3 ml (10 mmoles) of isobutyl chloroformate are added dropwise. After 15 minutes of stirring gaseous ammonia is introduced into the reaction mixture for 0.5 hours at -10° C., and then the mixture is allowed to stand at 0°-5° C. for 2 hours. The precipitate is filtered off, the filtrate is evaporated, and the oily residue is dissolved in 30 ml of chloroform. This solution is washed twice with 10 ml of n hydrochloric acid, each, twice with 10 ml of n sodium hydrocarbonate solution, each, and then with 10 ml of water, dried over anhydrous sodium sulfate, and evaporated. The oily residue is crystallized from n-hexane to obtain 1.95 g of a crude product. This crude product is recrystallized from a mixture of ethyl acetate and ether to obtain 1.78 g (78%) of BOC-HPro-NH2 ; m.p.: 138°-140° C., Rf2 =0.43, [α]D25 =-24.85° (c=1%, in acetic acid).

Workup

  1. filtrationThe precipitate is filtered off
  2. customthe filtrate is evaporated
  3. dissolutionthe oily residue is dissolved in 30 ml of chloroform
  4. washThis solution is washed twice with 10 ml of n hydrochloric acid
  5. dry with materialeach, twice with 10 ml of n sodium hydrocarbonate solution, each, and then with 10 ml of water, dried over anhydrous sodium sulfate
  6. customevaporated
  7. customThe oily residue is crystallized from n-hexane
  8. customto obtain 1.95 g of a crude product
  9. customThis crude product is recrystallized from a mixture of ethyl acetate and ether

Sources & evidence

ORD record
ord-8e3201e001db46bfac2b223c861e6188
Source dataset
uspto-grants-1983_05
Patent number
US04386073

Reaction notes

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