tert-Butyldimethylsilyl chloride → (+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)pipecolic acid methyl ester

HRID 751159노트

반응식

HRID 751159 반응식
[CH3:1][O:2][C:3](=[O:18])[C@@H:4]1[C@H:9]([OH:10])[CH2:8][CH2:7][CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].CCN(C(C)C)C(C)C.[Si:28](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3](=[O:18])[C@@H:4]1[C@H:9]([O:10][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH2:8][CH2:7][CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12]

참가 물질

6

반응물 3

HCID 28928tert-Butyldimethylsilyl chloride2회HCID 81531Diisopropylethylamine2회HCID 59754228rac-1-tert-butyl 2-methyl (2R,3S)-3-hydroxypiperidine-1,2-dicarboxylate

생성물 1

HCID 68458695(+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)pipecolic acid methyl ester수율 81%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

To a solution of 77C (3.3 g, 12.7 mmol) in DCM (50 mL) was added DIPEA (6.63 mL, 38.1 mmol), tert-butyldimethylsilyl chloride (3.83 g, 25.4 mmol, 2.0 equiv) and DMAP (310 mg, 5.24 mmol, 0.2 equiv). The resulting mixture was stirred at rt overnight. TLC showed no completion and therefore another 2.2 mL of DIPEA and 1.91 g of tert-butyldimethylsilyl chloride were added and stirred at rt for 3 days. The mixture was concentrated and the residue was diluted with EtOAc (100 mL), washed with 0.5 N HCl (2×30 mL), brine (2×30 mL), dried (MgSO4) and evaporated to give the crude product as a light pink oil. Purification of the crude product by flash chromatography (5-10% EtOAc/hexane) gave the desired product 77D (3.8 g, 81%): Rf (10% EtOAc/hexane) 0.25; HPLC (Phenomenex Luna 5 u C18 4.6×50 mm, linear gradient over 4 min) retention time 4.3 min (100%); MS (ES) m/z 374 [M+1]+.

후처리

  1. stirringstirred at rt for 3 days
  2. concentrationThe mixture was concentrated
  3. additionthe residue was diluted with EtOAc (100 mL)
  4. washwashed with 0.5 N HCl (2×30 mL), brine (2×30 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto give the crude product as a light pink oil
  8. customPurification of the crude product by flash chromatography (5-10% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-d4abe7f146a14cffb14f9b74c80d62bc
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07405234B2

반응 노트

불러오는 중…