Ammonia → (s)-1-n-boc-pipecolamide

HRID 1155090Notes

Reaction equation

HRID 1155090 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

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, and then 1.3 ml (10 mmoles) of isobutyl chloroformate are added dropwise at -10° C. After 15 minutes of stirring gaseous ammonia is passed through the mixture at -10° C. for 0.5 hours, and the resulting mixture is allowed to stand at 0°-5° C. for 2 hours. The separated precipitate is filtered off, the filtrate is evaporated, and the oily residue is dissolved in 30 ml of chloroform. The solution is shaken 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, and the resulting 1.96 g of crude product are recrystallized from a mixture of ethyl acetate and ether. 1.78 g (78%) of BOC-HPro-NH2 are obtained; m.p.: 138°-140° C., Rf2 =0.43, [α]D25 =-24.85° (c=1%, in acetic acid).

Workup

  1. filtrationThe separated precipitate is filtered off
  2. customthe filtrate is evaporated
  3. dissolutionthe oily residue is dissolved in 30 ml of chloroform
  4. 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
  5. customevaporated
  6. customThe oily residue is crystallized from n-hexane
  7. customthe resulting 1.96 g of crude product are recrystallized from a mixture of ethyl acetate and ether

Sources & evidence

ORD record
ord-16643655ef3a476cb128a68aa4c3be0a
Source dataset
uspto-grants-1981_11
Patent number
US04299821

Reaction notes

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