Cesium carbonate → methyl (5-{3-[2-propyl-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-1H-indol-1-yl)acetate

HRID 2424965Notes

Reaction equation

HRID 2424965 reaction equation
[CH2:1]([C:4]1[CH:9]=[C:8]([C:10]2[S:11][C:12]3[CH2:18][CH2:17][CH2:16][CH2:15][C:13]=3[N:14]=2)[CH:7]=[CH:6][C:5]=1[OH:19])[CH2:2][CH3:3].[CH3:20][O:21][C:22](=[O:38])[CH2:23][N:24]1[C:32]2[C:27](=[CH:28][C:29]([O:33][CH2:34][CH2:35][CH2:36]Br)=[CH:30][CH:31]=2)[CH:26]=[CH:25]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[CH3:20][O:21][C:22](=[O:38])[CH2:23][N:24]1[C:32]2[C:27](=[CH:28][C:29]([O:33][CH2:34][CH2:35][CH2:36][O:19][C:5]3[CH:6]=[CH:7][C:8]([C:10]4[S:11][C:12]5[CH2:18][CH2:17][CH2:16][CH2:15][C:13]=5[N:14]=4)=[CH:9][C:4]=3[CH2:1][CH2:2][CH3:3])=[CH:30][CH:31]=2)[CH:26]=[CH:25]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 57845410methyl [5-(3-bromopropoxy)-1H-indol-1-yl]acetateHCID 1359745042-Propyl-4-(4,5,6,7-tetrahydro-benzothiazol-2-yl)-phenol

Product 1

HCID 57845400methyl (5-{3-[2-propyl-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-1H-indol-1-yl)acetateYield 67.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Propyl-4-(4,5,6,7-tetrahydro-benzothiazol-2-yl)-phenol (Example 36, 0.75 g, 2.76 mmol) was combined with [5-(3-bromo-propoxy)-indol-1-yl]-acetic acid methyl ester (Example 47, 0.75 g, 2.30 mmol) in 12 mL DMF (containing 1 v/v % of water). To this mixture was added Cs2CO3 (1.50 g, 4.60 mmol), and the resulting mixture was allowed to stir at rt for 14 h. At this time, the reaction mixture was diluted with EtOAc (50 mL) and then washed three times with water (75 mL total). The water layers were extracted with EtOAc (25 mL) and the combined organic extracts were dried over MgSO4, filtered, and then concentrated under reduced pressure. Purification via flash silica gel chromatography (1:1 hexane/EtOAc) gave the title compound (800 mg, 64%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.75-7.70 (m, 2H), 7.18-7.10 (m, 2H), 7.05 (d, 1H), 6.92-6.85 (m, 2H), 6.48 (d, 1H), 4.84 (s, 2H), 4.30-4.20 (m, 4H), 3.75 (s, 3H), 2.90-2.75 (m, 4H) 2.70-2.60 (m, 2H), 2.40-2.30 (m, 2H), 1.95-1.85 (m, 4H), 1.70-1.58 (m, 2H), 0.95 (t, 3H).

Workup

  1. washwashed three times with water (75 mL total)
  2. extractionThe water layers were extracted with EtOAc (25 mL)
  3. dry with materialthe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification via flash silica gel chromatography (1:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-c9ed6eb2bc3e46fc90dcaa4d5e986a58
Source dataset
uspto-grants-2011_06
Patent number
US07964622B2

Reaction notes

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