Cesium carbonate → (2S)-3-(4-{3-[4-(1H-Indol-5-yl)-phenoxy]-propoxy}-phenyl)-2-methoxy-propionic acid ethyl ester

HRID 459289Notes

Reaction equation

HRID 459289 reaction equation
[CH2:1]([O:3][C:4](=[O:27])[C@@H:5]([O:25][CH3:26])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21](I)=[CH:20][CH:19]=2)=[CH:9][CH:8]=1)[CH3:2].[NH:28]1[C:36]2[C:31](=[CH:32][C:33](B(O)O)=[CH:34][CH:35]=2)[CH:30]=[CH:29]1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4](=[O:27])[C@@H:5]([O:25][CH3:26])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:33]3[CH:32]=[C:31]4[C:36](=[CH:35][CH:34]=3)[NH:28][CH:29]=[CH:30]4)=[CH:20][CH:19]=2)=[CH:9][CH:8]=1)[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343615-Indolylboronic acidHCID 58822720(2S)-3-{4-[3-(4-iodo-phenoxy)-propoxy]-phenyl}-2-methoxy-propionic acid ethyl ester

Product 1

HCID 58823023(2S)-3-(4-{3-[4-(1H-Indol-5-yl)-phenoxy]-propoxy}-phenyl)-2-methoxy-propionic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred mixture of (2S)-3-{4-[3-(4-iodo-phenoxy)-propoxy]-phenyl}-2-methoxy-propionic acid ethyl ester (0.10 mmol, 50 mg) (Step A), 5-indolyl-boronic acid (0.114 mmol, 18 mg) and powered cesium carbonate (0.23 mmol, 35 mg) in DME (0.5 mL) was added Pd(PPh3)4 (0.003 mmol, 4 mg). The mixture was flushed with nitrogen and maintained under nitrogen while being heated at reflux in a 100° C. oil bath. The mixture was stirred for 6 hours, and then cooled to room temperature and diluted with ethyl acetate and water. The organic layer was dried (Na2SO4) and concentrated. The crude product was purified by chromatography on silica gel (CH2Cl2/EtOAc 96:4) to afford the title compound 1H-NMR (CDCl3, 200.15 MHz): δ 8.20 (broad s, 1H), 7.80 (d, 1H, J=0.8), 7.56 (d, 3H, J=8.9), 7.41 (d, 2H, J=1.6), 7.23 (dd, 1H, J=3.2, 2.4), 7.15 (d, 3H, J=8.6), 6.99 (d, 2H, J=8.9), 6.85 (d, 3H, J=8.6), 6.60–6.58 (m, 1H), 4.24–4.11 (m, 8H), 3.92 (dd, 1H, J=7.3, 5.9), 3.35 (s, 4H), 2.98–2.94 (m, 3H), 2.28 (qn, 2H, J=5.9), 1.24 (t, 4H, J=7.3).

Workup

  1. customThe mixture was flushed with nitrogen
  2. temperaturemaintained under nitrogen
  3. temperaturewhile being heated
  4. temperaturecooled to room temperature
  5. additiondiluted with ethyl acetate and water
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude product was purified by chromatography on silica gel (CH2Cl2/EtOAc 96:4)

Sources & evidence

ORD record
ord-e6b05e7cb757469a8114d90316cf91e4
Source dataset
uspto-grants-2007_03
Patent number
US07192982B2

Reaction notes

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