苯甲酸 → (3S,5S)-N-Boc-5-ethynyl-3-hydroxy-pyrrolidine

HRID 1069757笔记

反应方程式

HRID 1069757 反应方程式
[C:1]([N:8]1[C@H:12]([C:13]#[CH:14])[CH2:11][C@@H:10]([OH:15])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(O)(=O)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C([O-])([O-])=O.[K+].[K+]>C1COCC1>[C:1]([N:8]1[C@H:12]([C:13]#[CH:14])[CH2:11][C@H:10]([OH:15])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

参与物

7

反应物 5

HCID 243苯甲酸HCID 11430碳酸钾HCID 11776三苯基膦HCID 75555偶氮二甲酸二异丙酯HCID 11816659tert-butyl (2S,4R)-2-ethynyl-4-hydroxypyrrolidine-1-carboxylate

产物 1

HCID 21971746(3S,5S)-N-Boc-5-ethynyl-3-hydroxy-pyrrolidine

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂

实验过程

To a solution of (3R,5S)-N-Boc-3-Hydroxy-5-ethynyl-pyrrolidine (200 mg, 0.95 mmol) (Example 99C), benzoic acid (138 mg, 0.11 mmol) and triphenyl phosphine (373 mg, 1.42 mmol) in 15 mL of THF was added diisopropyl azodicarboxylate (287 mg, 1.42 mmol) at 0° C. The mixture was allowed to slowly warm up to room temperature and stirred for 18 hrs. The reaction mixture was then concentrated and the residue was directly passed through a silica gel column with a 0-30% EtOAc in hexanes gradient. The intermediate benzoate ester was dissolved in 6 mL of MeOH and then K2CO3 (260 mg, 1.89 mmol) was added. The mixture, after overnight stirring, was filtered and concentrated to a residue which after silica gel column chromatography with a 0-70% EtOAc in hexanes gradient afforded (3S,5S)-N-Boc-5-ethynyl-3-hydroxy-pyrrolidine. (Yield 170 mg, 85%).

后处理

  1. concentrationThe reaction mixture was then concentrated
  2. dissolutionThe intermediate benzoate ester was dissolved in 6 mL of MeOH
  3. stirringThe mixture, after overnight stirring
  4. filtrationwas filtered
  5. concentrationconcentrated to a residue which after silica gel column chromatography with a 0-70% EtOAc in hexanes gradient

来源与证据

ORD记录
ord-ef14a91020a744ab9987b24ef6683695
来源数据集
uspto-grants-2001_06
专利号
US06252086B1

反应笔记

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