Benzyl Bromide → (1R,2S)-2-(1-benzyl-3-iodo-1H-indazol-6-yl)-1'-methylspiro[cyclopropane-1,3'-indolin]-2'-one

HRID 1410364Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1410364
[I:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[N:15]([CH3:22])[C:14]4=[O:23])[CH2:12]3)=[CH:8][CH:9]=2)[NH:4][N:3]=1.[OH-].[K+].[CH:26]1[CH:31]=[CH:30][C:29]([CH2:32]Br)=[CH:28][CH:27]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[CH2:32]([N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[C:7]([C@H:11]3[C@@:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[N:15]([CH3:22])[C:14]4=[O:23])[CH2:12]3)[CH:6]=2)[C:2]([I:1])=[N:3]1)[C:29]1[CH:30]=[CH:31][CH:26]=[CH:27][CH:28]=1

Komponenten

6

Edukt 3

HCID 7498Benzyl BromideHCID 14797Potassium HydroxideHCID 178481340HCID 178481340, Verbindung

Produkt 1

HCID 86681514(1R,2S)-2-(1-benzyl-3-iodo-1H-indazol-6-yl)-1'-methylspiro[cyclopropane-1,3'-indolin]-2'-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 74236Tetrabutylammonium BromideKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A round-bottom flask was charged with (1R,2S)-2-(3-iodo-1H-indazol-6-yl)-1′-methylspiro[cyclopropane-1,3′-indolin]-2′-one (200 mg, 0.482 mmol), tetrabutylammonium bromide (2.0 mg, 0.005 mmol), CH2Cl2 (3.5 mL), and KOH (1.0 mL, 50% wt aqueous solution). The mixture was then treated with BnBr (69 uL, 0.578 mmol) and the reaction stirred for 18 h at which time the product was extracted with CH2Cl2 (3×) and the combined organic layers washed with brine and dried over MgSO4. After removal of solvent, purification using a Biotage Isolera (silica gel, 1-5% MeOH in DCM) gave the title compound. 1H NMR (400 MHz, CDCl3) δ 7.35 (d, 1H, J=8.2 Hz), 7.29-7.25 (m, 3H), 7.15-7.10 (m, 4H), 6.97 (d, 1H, J=8.3 Hz), 6.85 (d, 1H, J=8.0 Hz), 6.56 (t, 1H, J=7.3 Hz), 5.72 (d, J=7.5 Hz, 1H), 5.63-5.49 (m, 2H), 3.39 (t, J=8.8 Hz, 1H), 3.32 (s, 3H), 2.22-2.19 (m, 1H), 1.97-1.94 (m, 1H); MS ESI 506.1 [M+H]+, calcd for [C25H20IN3O+H]+ 506.07. Recrystallization from neat MeOH yielded clear, colorless crystals which were submitted for single crystal X-ray structure determination. The structure obtained (see FIGURE) confirmed the relative and absolute stereochemistry as (1R,2S), i.e. identical to that predicted by the “Sharpless mnemonic”. The crystallographic data is summarized in the table below.

Aufarbeitung

  1. extractionwas extracted with CH2Cl2 (3×)
  2. washthe combined organic layers washed with brine
  3. dry with materialdried over MgSO4
  4. customAfter removal of solvent, purification

Quellen und Nachweise

ORD-Eintrag
ord-a6906e24e2904d2eb47f23b73d9f9f05
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08921545B2

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