Cesium carbonate → ethyl ((1S)-5-{3-[2-propoxy-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-2,3-dihydro-1h-inden-1-yl)acetate

HRID 2235900Notes

Reaction equation

HRID 2235900 reaction equation
[OH:1][C:2]1[CH:27]=[C:26]([C:28]2[S:29][C:30]3[CH2:36][CH2:35][CH2:34][CH2:33][C:31]=3[N:32]=2)[CH:25]=[CH:24][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[C@H:14]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:13][CH2:12]2.C([O-])([O-])=O.[Cs+].[Cs+].I[CH2:44][CH2:45][CH3:46]>CN(C=O)C.O>[CH2:44]([O:1][C:2]1[CH:27]=[C:26]([C:28]2[S:29][C:30]3[CH2:36][CH2:35][CH2:34][CH2:33][C:31]=3[N:32]=2)[CH:25]=[CH:24][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[C@H:14]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:13][CH2:12]2)[CH2:45][CH3:46]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 336431-IodopropaneHCID 59300497ethyl ((1S)-5-{3-[2-hydroxy-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2yl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 59300423ethyl ((1S)-5-{3-[2-propoxy-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-2,3-dihydro-1h-inden-1-yl)acetateYield 91.2%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6228DimethylformamideSolvent

Procedure

Ethyl ((1S)-5-{3-[2-hydroxy-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)-phenoxy]-propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 165, 90 mg, 0.177 mmol) was dissolved in DMF (3 mL) after which Cs2CO3 (69.3 mg, 0.213 mmol) and water (3 drops) were added. Iodopropane (0.02 mL, 0.213 mmol) was added to the flask, and the reaction mixture was stirred at room temperature for 18 h. The mixture was then filtered and the filtrate purified by preparative HPLC giving the desired ester as a white solid (88.7 mg, 91%). 1H NMR (400 MHz, CD2Cl2): δ 7.47 (s, 1H), 7.37 (dd, 1H), 7.05 (d, 1H), 6.93 (d, 1H), 6.79 (s, 1H), 6.71 (dd, 1H), 4.23 (t, 2H), 4.19-4.13 (m, 4H), 4.03 (t, 2H), 3.50 (m, 1H), 2.94-2.78 (m, 6H), 2.70 (dd, 1H), 2.44-2.25 (m, 4H), 1.92-1.70 (m, 7H), 1.28 (t, 3H), 1.07 (t, 3H).

Workup

  1. additionwere added
  2. filtrationThe mixture was then filtered
  3. customthe filtrate purified by preparative HPLC

Sources & evidence

ORD record
ord-c7200d6ade6f4ce6a9c4709c7d5cfda5
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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