Cesium carbonate → HCID 67496634, compound

HRID 1628316Notes

Reaction equation

HRID 1628316 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=2)=[CH:4][C:3]=1[NH:15][C:16](=[O:32])[C@@H:17]([NH:25][CH2:26][C:27]1[N:28]=[CH:29][S:30][CH:31]=1)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Br[CH2:34][C:35]([O:37][CH3:38])=[O:36].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:14][C:10]1[CH:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([O:1][CH2:34][C:35]([O:37][CH3:38])=[O:36])=[C:3]([NH:15][C:16](=[O:32])[C@@H:17]([NH:25][CH2:26][C:27]3[N:28]=[CH:29][S:30][CH:31]=3)[CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:4]=2)[CH:13]=[CH:12][N:11]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 60984Methyl bromoacetateHCID 136391028HCID 136391028, compound

Product 1

HCID 67496634HCID 67496634, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Phenol 64.D (248 mg, 0.56 mmol), methyl 2-bromoacetate (85 mg, 0.56 mmol), and Cs2CO3 (182 mg, 0.56 mmol) were mixed in DMF (1 ml) and stirred at room temperature for 1 h. The reaction mixture was partitioned with EtOAc/H2O and the aqueous layer was exctracted with EtOAc (3×). The organic layers were combined, dried with sodium sulfate, filtered, and concentrated. The crude product was first purified on a silica gel column (12 g, 0-10% MeOH:DCM) and then by prepHPLC(C18, ACN:H2O:0.1% TFA, gradient). The desired fractions were combined, partially concentrated on a rotavap, neutralized with NaHCO3 (sat), and extracted with DCM (2×). The organic layers were combined, dried with sodium sulfate, filtered, and concentrated to yield 64 (190 mg, 66%). LC-MS (+esi, M+H+=517.2). 1H NMR (400 MHz, MeOH) δ ppm 8.86 (d, J=1.96 Hz, 1H) 8.59 (d, J=2.35 Hz, 1H) 8.42 (d, J=5.09 Hz, 1H) 7.56 (s, 1H) 7.46-7.51 (m, 2H) 7.34 (d, J=1.96 Hz, 1H) 7.19-7.30 (m, 5H) 7.09 (d, J=8.61 Hz, 1H) 4.84 (s, 2H) 3.85-4.02 (m, 2H) 3.78 (s, 3H) 3.59 (dd, J=8.41, 4.89 Hz, 1H) 3.19 (dd, J=13.69, 5.09 Hz, 1H) 2.92 (dd, J=13.69, 8.61 Hz, 1H) 2.60 (s, 3H).

Workup

  1. customThe reaction mixture was partitioned with EtOAc/H2O
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was first purified on a silica gel column (12 g, 0-10% MeOH:DCM)
  6. concentrationpartially concentrated on a rotavap
  7. extractionextracted with DCM (2×)
  8. dry with materialdried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-06d7ff4cf1c84689a39c17c29c079e26
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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