Piperidine → 3-Amino-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid

HRID 1867753노트

반응식

HRID 1867753 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH:17]C(OCC2C3C=CC=CC=3C3C2=CC=CC=3)=O)([C:14]([OH:16])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC)(C)(C)C.C(O)(C)C.N1CCCCC1>CN(C)C=O>[NH2:17][C:10]1([C:14]([OH:16])=[O:15])[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1

참가 물질

5

반응물 3

HCID 8082PiperidineHCID 27344081-((tert-butoxy)carbonyl)-3-(((9H-fluoren-9-ylmethoxy)carbonyl)amino)piperidine-3-carboxylic acid2회HCID 86616950TBME isopropanol

생성물 1

HCID 247296423-Amino-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid수율 81%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

1-(tert-butoxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}piperidine-3-carboxylic acid was resolved by chiral HPLC resolution {Merck 50 mm 16 μm Kromasil Chirose 2 No. CT9014, tert-butylmethylether/iso-propanol (90/10). The first eluted enantiomer (800 mg, 1.71 mmol) 1-(tert-butoxycarbonyl)-3-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}piperidine-3-carboxylic acid (Isomer 1) was dissolved in N,N-dimethylformamide (10 ml) and piperidine (0.85 ml, 8.55 mmol) added. The mixture was stirred at room temperature over night. The resulting white precipitate was filtered off. The filtrates were concentrated and the residues purified by column chromatography on silica eluting with saturated ammonia in methanol/dichloromethane (25/75). The fractions containing the desired product were combined with the filtered solids and evaporated to give 3-amino-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (Isomer 1) (339 mg, 81%); 1H NMR Spectrum: (D2O) 1.44 (s, 9H); 1.63 (m, 1H); 1.79 (d, 1H); 1.97 (d, 1H); 2.10 (m, 1H); 2.88 (t, 1H); 3.33 (d, 1H); 4.09 (m, 2H).

후처리

  1. filtrationThe resulting white precipitate was filtered off
  2. concentrationThe filtrates were concentrated
  3. customthe residues purified by column chromatography on silica eluting with saturated ammonia in methanol/dichloromethane (25/75)
  4. additionThe fractions containing the desired product
  5. customevaporated

출처 및 근거

ORD 기록
ord-fd232c69c90944ada391054ec49e10f5
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07632840B2

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