Acetic Acid → 2-[3-(1-Piperidinylmethyl)-2-pyridinyl]-1H-isoindole-1,3(2H)-dione

HRID 460169Notes

Reaction equation

Br[CH:2](Br)[C:3]1[C:4]([N:9]2[C:13](=[O:14])[C:12]3=[CH:15][CH:16]=[CH:17][CH:18]=[C:11]3[C:10]2=[O:19])=[N:5][CH:6]=[CH:7][CH:8]=1.[NH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CCOC(C)=O>[C:13]1(=[O:14])[N:9]([C:4]2[C:3]([CH2:2][N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:8][CH:7]=[CH:6][N:5]=2)[C:10](=[O:19])[C:11]2=[CH:18][CH:17]=[CH:16][CH:15]=[C:12]12

Participants

Conditions

Temperature: 23 °C

Procedure

3-(Dibromomethyl)-2-(phthalimidyl)pyridine (185 mg, 0.47 mmol) was dissolved in CH2Cl2 (2 mL) and treated with piperidine (0.460 mL, 4.66 mmol), and glacial AcOH (0.160 mL, 2.80 mmol) in a dropwise fashion. The resulting yellow solution was stirred at 23° C. for 2 h, then treated with solid NaBH(OAc)3 (393 mg, 1.86 mmol) in one portion, and stirring was continued for 14 h. After stirring 14 h at 23° C., the mixture was treated with 2M K2CO3 (6 mL), and stirred for 1 h. After 1 h, the mixture was diluted with EtOAc (50 mL) and washed with H2O (1×50 mL), and saturated NaCl (1×50 mL). The organic phase was then dried (MgSO4) and concentrated in vacuo to provide the title compound as a yellow residue. The crude material was used in subsequent transformations without further purification. MS m/z: 323 (M+H).

Workup

stirringstirring
waitwas continued for 14 h
stirringAfter stirring 14 h at 23° C.
stirringstirred for 1 h
waitAfter 1 h
washwashed with H2O (1×50 mL), and saturated NaCl (1×50 mL)
dry with materialThe organic phase was then dried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-1eea4131d09846b88e1af5b8eb84595b
Source dataset: uspto-grants-2007_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07196104B2

Reaction notes

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