Sodium Cyanide → (1R,2R)-methyl-3-((2-(4-cyanophenyl)-5'-fluoro-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoate

HRID 1805311노트

반응식

HRID 1805311 반응식
[CH3:1][O:2][C:3](=[O:34])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][C:16]([F:20])=[CH:17][CH:18]=3)[C@:13]3([CH2:22][C@:21]3([C:26]3[CH:31]=[CH:30][C:29](I)=[CH:28][CH:27]=3)[CH:23]([CH3:25])[CH3:24])[C:12]2=[O:33])[CH:5]=1.[C-:35]#[N:36].[Na+]>O1CCCC1.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:34])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][C:16]([F:20])=[CH:17][CH:18]=3)[C@:13]3([CH2:22][C@:21]3([C:26]3[CH:31]=[CH:30][C:29]([C:35]#[N:36])=[CH:28][CH:27]=3)[CH:23]([CH3:25])[CH3:24])[C:12]2=[O:33])[CH:5]=1

참가 물질

6

반응물 2

HCID 8929Sodium CyanideHCID 58305329(1R,2R)-methyl-3-((-5'-fluoro-2-(4-iodophenyl)-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoate

생성물 1

HCID 67235156(1R,2R)-methyl-3-((2-(4-cyanophenyl)-5'-fluoro-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoate수율 45.5%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of (1S,2S) and (1R,2R)-methyl-3-((-5′-fluoro-2-(4-iodophenyl)-2-isopropyl-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)methyl)benzoate (1.35 g, 2.4 mmol), NaCN (240 mg, 4.9 mmol), CuI (50 mg, 0.3 mmol) and Pd(PPh3)4 (140 mg, 0.12 mmol) in tetrahydrofuran (9.0 mL) was stirred at 65° C. for 2 hours. The mixture was cooled to room temperature and extracted with ethyl acetate and washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo. Purification by flash column chromatography eluting with Hexane/ethyl acetate (8:1 to 4:1) to afford light yellow oil (500 mg, yield 45.5%) LC/MS m/e calcd. for C29H25FN2O3: 469, observed (M+H)+: 469.2

후처리

  1. extractionextracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by flash column chromatography
  6. washeluting with Hexane/ethyl acetate (8:1 to 4:1)

출처 및 근거

ORD 기록
ord-e7a9ea233f9e41978830b482c75003cc
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354443B2

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