Ethyl bromoacetate → HCID 67409555, compound

HRID 1949640Notes

Reaction equation

HRID 1949640 reaction equation
COC([N:5]1[CH2:9][CH:8]([C:10]2[C:18]3[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[CH:7]2[N:20]([C:23](=[O:39])[CH:24]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:21][CH2:22][CH:6]12)=O.C([O-])([O-])=O.[K+].[K+].Br[CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49]>C(#N)C.O>[CH2:51]([O:50][C:48](=[O:49])[CH2:47][N:5]1[CH2:9][CH:8]([C:10]2[C:18]3[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[CH:7]2[N:20]([C:23](=[O:39])[CH:24]([NH:31][C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:21][CH2:22][CH:6]12)[CH3:52]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 674097574-(2-tert-Butoxycarbonylamino-2-cyclohexyl-acetyl)-3-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid methyl ester

Product 1

HCID 67409555HCID 67409555, compoundYield 82.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A solution containing amine 50 (200 mg, 0.41 mmol) in ACN (5 mL) was cooled to 0° C. K2CO3 (63 mg, 0.46 mmol) was added followed by ethyl bromoacetate (75 mg, 0.45 mmol) and the reaction mixture was warmed to ambient temperature. After 16 h, the reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (1:1 hexanes/EtOAc) to afford 194 mg (82%) of 58 as an off-white-colored foam. 1H NMR (300 MHz, CDCl3), mixture of amide rotamers: δ8.50 (s, 0.8H), 8.29 (s, 0.2H), 7.55 (dd, J=5.4, 8.7 Hz, 1H), 7.11 (s, 1H), 6.99 (d, J=9.0 Hz, 0.2H), 6.82 (d, J=9.6 Hz, 0.8H), 5.30-5.24 (m, 1H), 4.85-4.82 (m, 1H), 4.34 (t, J=6.0 Hz, 1H), 4.23-4.07 (m, 2H), 3.93 (t, J=8.7 Hz, 1H), 3.68-3.64 (m, 2H), 3.59-3.54 (m, 2H), 3.44-3.40 (m, 2H), 2.82 (app t, J=9.0 Hz, 1H), 2.05-2.01 (m, 1H), 1.83-1.65 (m, 6H), 1.38 (s, 9H), 1.28 (t, J=6.9 Hz, 3H), 1.24-1.05 (m, 2H) ppm. Mass spectrum, m/z [571.4] (M+H)+.

Workup

  1. temperaturethe reaction mixture was warmed to ambient temperature
  2. extractionextracted with EtOAc
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash silica gel chromatography (1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-41da31a680034e63a87a1201bf1e4373
Source dataset
uspto-grants-2013_03
Patent number
US08399683B2

Reaction notes

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