Benzoic Acid → (3S,5S)-N-Boc-5-ethynyl-3-hydroxy-pyrrolidine

HRID 1069757노트

반응식

HRID 1069757 반응식
[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]

참가 물질

7

반응물 5

HCID 243Benzoic AcidHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 11816659tert-butyl (2S,4R)-2-ethynyl-4-hydroxypyrrolidine-1-carboxylate

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-ef14a91020a744ab9987b24ef6683695
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06252086B1

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