Sodium Bicarbonate → (2S)-5-[(benzyloxy)amino]-2-cyanopiperidine

HRID 517672

반응식

HRID 517672 반응식
C(O)(=O)C(O)=O.[CH2:7]([O:14][NH:15][CH:16]1[CH2:21][NH:20][C@H:19]([C:22]#[N:23])[CH2:18][CH2:17]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O>[CH2:7]([O:14][NH:15][CH:16]1[CH2:21][NH:20][C@H:19]([C:22]#[N:23])[CH2:18][CH2:17]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

참가 물질

4

반응물 2

HCID 516892Sodium BicarbonateHCID 131732538(2S)-5-[(benzyloxy)amino]-2-cyanopiperidine ethanedioate

생성물 1

HCID 117599345(2S)-5-[(benzyloxy)amino]-2-cyanopiperidine

시약·촉매·용매 1

HCID 22728543Water ethylacetate용매

실험 절차

To a stirred suspension of (2S)-5-[(benzyloxy)amino]-2-cyanopiperidine ethanedioate (1:1) (XI) (3.7 gm, 0.0115 mol, prepared according to the procedure described in step 8) in ethyl acetate:water (1:1, 37 ml:37 ml) was added solid sodium bicarbonate (1.9 gm, 0.022 mol) at 25° C. After 30 minutes of stirring the organic layer was separated. The aqueous layer was re-extracted with ethyl acetate (20 ml). The combined organic layer was washed with water (20 ml) and brine (20 ml), dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain 3 gm of ((2S)-5-[(benzyloxy)amino]-2-cyanopiperidine (XII) as an oil. The oily product, (2S)-5-[(benzyloxy)amino]-2-cyanopiperidine (XII) (1 gm, 0.00432 mol, prepared as mentioned above), was dissolved in acetonitrile (ACN) (15 ml), cooled to 10° C., stirred and triethyl amine (1.8 ml, 0.0129 mol) was added in one portion. To this mixture was added slowly a solution of triphosgene (0.564 gm, 0.0019 mol) in acetonitrile (6 ml). After 15 minutes of stirring, DMAP (0.0527 gm, 0.000432 mol) was added and the reaction mixture allowed to warm to 25° C. After 16 hours of stirring, the thin layer chromatography (ethyl acetate:hexane (1:1)) showed the two separable mixture of isomers. A solution of saturated sodium bicarbonate (10 ml) was added to the reaction mass and stirring continued for another 30 minutes. The volatiles were removed under reduced pressure. The residual mass was partitioned between ethyl acetate (10 ml) and water (10 ml). The organic layer was separated and the aqueous layer re-extracted with ethyl acetate (10 ml). The combined organic layer was washed with water (10 ml) and brine (10 ml), dried over anhydrous sodium sulphate and the solvent evaporated under reduced pressure. The resulting mixture was dissolved in dichloromethane (15 ml) and washed with 5% potassium hydrogen sulphate solution (3×10 ml), saturated sodium hydrogen carbonate (10 ml) and water (10 ml). The organic layer was concentrated under reduced pressure, to yield 0.610 gm of crude oily product.

후처리

  1. customprepared
  2. customwas separated
  3. extractionThe aqueous layer was re-extracted with ethyl acetate (20 ml)
  4. washThe combined organic layer was washed with water (20 ml) and brine (20 ml)
  5. dry with materialdried over anhydrous sodium sulphate
  6. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-b498c4d75f8748bea8c542548572bbea
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115131B2

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