Ammonium Chloride → HCID 131729447, compound

HRID 1641410Notes

Reaction equation

HRID 1641410 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[C:6]([O:10][C:11](=[O:22])[NH:12][C@H:13]([C:15]1[CH:20]=[CH:19][C:18](Br)=[CH:17][N:16]=1)[CH3:14])([CH3:9])([CH3:8])[CH3:7].[Cl-].[NH4+]>C1COCC1.[Zn+2].[Br-].[Br-].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>[C:6]([O:10][C:11](=[O:22])[NH:12][C@H:13]([C:15]1[CH:20]=[CH:19][C:18]([CH:1]2[CH2:3][CH2:2]2)=[CH:17][N:16]=1)[CH3:14])([CH3:9])([CH3:8])[CH3:7]

Participants

7

Reactant 3

HCID 25517Ammonium ChlorideHCID 904516721,1-Dimethylethyl N-[(1S)-1-(5-bromo-2-pyridinyl)ethyl]carbamateHCID 178418630HCID 178418630, compound

Product 1

HCID 131729447HCID 131729447, compoundYield 78.1%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of ZnBr2 (7.85 g, 34.9 mmol) in THF (40 ml) was added cyclopropylmagnesium bromide (54.8 ml, 27.4 mmol) in THF dropwise at −78° C. After stirring at −78° C. for 30 minutes, the resulting solution was warmed to 0° C. and stirred at 0° C. for 30 minutes. (S)-tert-Butyl-1-(5-bromopyridin-2-yl)ethylcarbamate (Method 27; 3.00 g, 9.96 mmol) and Pd(PPh3)4 (0.576 g, 0.498 mmol) were added successively. The resulting mixture was stirred at 60° C. for 3 hours. After cooled to room temperature, 100 ml of saturated ammonium chloride was added, extracted with EtOAc and dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane-EtOAc=4:1) to give the title compound as a white solid (2.04 g, 78%). 1H NMR (400 MHz) δ 8.30 (d, J=2.0 Hz, 1H), 7.37 (dd, J=1.6 and 8.0 Hz, 1H), 7.25 (d, J=7.6 Hz, 1H), 7.20 (d, J=8.4 Hz, 1H), 4.61 (m, 1H), 1.92 (m, 1H), 1.37 (s, 9H), 1.29 (d, J=7.2 Hz, 3H), 0.96 (m, 2H), 0.69 (m, 2H). MS: Calcd.: 262. Found: [M+H]+263.

Workup

  1. temperaturethe resulting solution was warmed to 0° C.
  2. stirringstirred at 0° C. for 30 minutes
  3. stirringThe resulting mixture was stirred at 60° C. for 3 hours
  4. temperatureAfter cooled to room temperature
  5. extractionextracted with EtOAc
  6. dry with materialdried over sodium sulfate
  7. customAfter removal of solvent
  8. customthe resulted residue was purified by column chromatography (hexane-EtOAc=4:1)

Sources & evidence

ORD record
ord-52c602330a2e4db5a2d4e2f2560f7a4f
Source dataset
uspto-grants-2012_02
Patent number
US08114989B2

Reaction notes

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