Ethyl Bromide → HCID 58935417, compound

HRID 855559Notes

Reaction equation

HRID 855559 reaction equation
[C:1]([CH2:4][N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C@H:7]([NH:16][C:17]([C:19]2([CH2:24][CH:25]([CH2:29][C:30]([NH:32][CH2:33][CH2:34][CH2:35][OH:36])=[O:31])[C:26]([OH:28])=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])[C:6]1=[O:37])([OH:3])=[O:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH2:44](Br)[CH3:45]>CN(C)C=O.O.ClCCl>[CH2:44]([O:2][C:1](=[O:3])[CH2:4][N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C@H:7]([NH:16][C:17]([C:19]2([CH2:24][CH:25]([CH2:29][C:30]([NH:32][CH2:33][CH2:34][CH2:35][OH:36])=[O:31])[C:26]([OH:28])=[O:27])[CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:18])[C:6]1=[O:37])[CH3:45]

Participants

7

Reactant 3

HCID 6332Ethyl BromideHCID 10796Cesium carbonateHCID 58935428HCID 58935428, compound

Product 1

HCID 58935417HCID 58935417, compoundYield 28,576.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

800 mg of the 2-{[1-({[(3S)-1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino}carbonyl)cyclopentyl]methyl}-4-[(3-hydroxypropyl)amino]-4-oxobutyric acid (isomer mixture) obtained above according to Example 9 was dissolved in 15 ml dimethyl formamide (=DMF). 302.5 mg Cs2CO3 and 169 mg ethyl bromide were added to this receiving solution at room temperature with stirring. After stirring overnight, it was diluted with 42 ml water and 21 ml dichloromethane and the aqueous phase was extracted with dichloromethane. The solvent was largely evaporated at reduced pressure and the remaining residue was chromatographed (stationary phase: silica gel, mobile phase: EA (100%) to EE/MeOH 7:3 (v/v)). Drying the product fractions in an oil pump vacuum (5×10−2 mbar) yielded 241 g of the title compound as foam resin, MS: [M+H]+: 546; m/z: 453, 425, 379; 1H-NMR (CDCl3): 7.34-7.1, m, [4]; 4.82, 4.77, 4.34, 4.29, AB-Q-. [2]; 3.62, m, [2]; 3.37, m, [3].

Workup

  1. stirringAfter stirring overnight
  2. extractionthe aqueous phase was extracted with dichloromethane
  3. customThe solvent was largely evaporated at reduced pressure
  4. customthe remaining residue was chromatographed (stationary phase: silica gel, mobile phase: EA (100%) to EE/MeOH 7:3 (v/v))
  5. customDrying the product fractions in an oil pump vacuum (5×10−2 mbar)

Sources & evidence

ORD record
ord-ae0b8833d2c54dfa9b92393d3800b78d
Source dataset
uspto-grants-2007_08
Patent number
US07262184B2

Reaction notes

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