Cesium carbonate → ethyl {(1S)-5-[3-(4-cyano-2-methoxyphenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl)acetate

HRID 603419Notes

Reaction equation

[OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][CH3:11].Br[CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[C@H:22]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:21][CH2:20]2.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([O:1][CH2:13][CH2:14][CH2:15][O:16][C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[C@H:22]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:21][CH2:20]3)=[C:3]([O:10][CH3:11])[CH:4]=1)#[N:7]

Participants

Conditions

Temperature: 40 °C

Procedure

To a mixture of 4-hydroxy-3-methoxybenzonitrile (2.6 g, 17.6 mmol), ethyl [(1S)-5-(3-bromopropoxy)-2,3-dihydro-1H-inden-1-yl]acetate (Example 45) (6 g, 17.6 mmol), and Cs2CO3 (6.9 g, 21.1 mmol) in DMF (30 mL) was added water (15 drops). The reaction mixture was stirred at 40° C. for 16 h and concentrated under reduced pressure. The residue was diluted with water and extracted with EtOAc (2×). The combined organic phases were dried over MgSO4, filtered, and concentrated under reduced pressure. Recrystallization from MeOH (5 mL) gave 4.9 g (68%) of the title compound as an off-white solid. LC-MS: RT=3.59 min; (M+H)+ 410.0.

Workup

concentrationconcentrated under reduced pressure
additionThe residue was diluted with water
extractionextracted with EtOAc (2×)
dry with materialThe combined organic phases were dried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customRecrystallization from MeOH (5 mL)

Sources & evidence

ORD record: ord-ffd4933d7d784d13b5ef9601d7870d13
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07906653B2

Reaction notes

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