Dimethyl Sulfoxide → (1R,3S,4S)-3-Formyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 882793노트

반응식

HRID 882793 반응식
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[C@H:23]([CH2:24][OH:25])[C@@H:22]2[CH2:26][C@H:19]1[CH2:20][CH2:21]2)=[O:17])([CH3:14])([CH3:13])[CH3:12].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:11]([O:15][C:16]([N:18]1[C@H:23]([CH:24]=[O:25])[C@@H:22]2[CH2:26][C@H:19]1[CH2:20][CH2:21]2)=[O:17])([CH3:14])([CH3:12])[CH3:13]

참가 물질

6

반응물 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 66866104tert-butyl (1R,3S,4S)-3-(hydroxymethyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

생성물 1

HCID 18396214(1R,3S,4S)-3-Formyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a cold (−60° C.) solution of oxalyl chloride (60.8 mmol) in dry DCM (130 mL) is added dropwise DMSO (111 mmol) within 5 min. After 15 min a solution of (1R,3S,4S)-3-hydroxymethyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (50.7 mmol) in dry DCM (40 mL) is added dropwise within 15 min. Stirring is continued for 45 min at −55° C., then DIPEA (253 mmol; dried over 3 A molecular sieve) is added during 5 min. The reaction mixture is allowed to reach rt and diluted with water (250 mL). The layers are separated and the organic layer is washed twice with aq. citric acid (5%, 200 mL each) and twice with brine. The combined organic layers are dried over MgSO4 and concentrated in vacuo to give the desired product which is used without further purification. 1H-NMR (CDCl3, 2 rotamers): δ=1.31-1.37 (m, 1H); 1.44 & 1.50 (2 s, 9H); 1.58-1.84 (m, 5H); 2.78 & 2.81 (2 bs, 1H); 3.60 & 3.74 (2 bs, 1H); 4.26 & 4.41 (2 bs, 1H); 9.55 & 9.60 (2 bs, 1H).

후처리

  1. customdried over 3 A molecular sieve)
  2. additionis added during 5 min
  3. customto reach rt
  4. additiondiluted with water (250 mL)
  5. customThe layers are separated
  6. washthe organic layer is washed twice with aq. citric acid (5%, 200 mL each) and twice with brine
  7. dry with materialThe combined organic layers are dried over MgSO4
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-bbd6503854b44a5fa64ecba10592f446
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08236801B2

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