1,4-Dioxaspiro[4.5]decan-8-one → 8-(6-Cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)-1,4-dioxaspiro[4,5]decane
Reaction equation
[CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]2)[O:3][CH2:2]1.[C:12]([C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[CH2:20][NH:19][CH2:18][CH2:17]2)#[N:13].C([BH3-])#N.[Na+]>>[C:12]([C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[CH2:20][N:19]([CH:7]1[CH2:8][CH2:9][C:4]3([O:11][CH2:1][CH2:2][O:3]3)[CH2:5][CH2:6]1)[CH2:18][CH2:17]2)#[N:13]Participants
4
Procedure
A solution of cyclohexane-1,4-dione monoethylene ketal(5.3 g, 33.9 mmole) and 6-cyano-1,2,3,4-tetrahydro-isoquinoline (5.3 g, 28.5 mmole) was treated with sodium cyanoborohydride (2.13 g, 33.8 mmole)at room temperature and stirred at ambient temperature for 18 hr. The reaction was concentrated to 1/4 volume at reduced pressure and poured into sat. NaHCO3 (500 ml ) and extracted with EtOAc (3×500 ml ). The combined organic layers were dried over anhydrous MgSO4 and evaporated under reduced pressure. The resulting foam was chromatographed on silica gel, eluting with 50% ethyl acetate/hexane to give 7.01 of product as a white solid which was recrystallized from ethanol. MP=127° C.
Workup
- concentrationThe reaction was concentrated to 1/4 volume at reduced pressure
- additionpoured into sat. NaHCO3 (500 ml )
- extractionextracted with EtOAc (3×500 ml )
- dry with materialThe combined organic layers were dried over anhydrous MgSO4
- customevaporated under reduced pressure
- customThe resulting foam was chromatographed on silica gel
- washeluting with 50% ethyl acetate/hexane
- customto give 7.01 of product as a white solid which
- customwas recrystallized from ethanol
Sources & evidence
- ORD record
- ord-5711b79ee22d4f08b5dbc1f6be737f0f
- Source dataset
- uspto-grants-1995_04
- Patent number
- US05403846
Reaction notes
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