Water → tert-Butyl N-[(1S)-1-[4-(2-aminophenyl)pyridin-2-yl]but-3-en-1-yl]carbamate

HRID 1481288Notes

Reaction equation

HRID 1481288 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@@H:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:9][CH:10]=[CH2:11])[CH:3]=1.[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O.O.P(=O)(O)(O)O.[K]>CS(C)=O.CCOC(C)=O.CCOCC>[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@@H:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:9][CH:10]=[CH2:11])[CH:3]=1

Participants

8

Reactant 5

HCID 962WaterHCID 1004Phosphoric AcidHCID 2773216(2-Aminophenyl)boronic acidHCID 5462222PotassiumHCID 66744734Carbamic acid, N-[(1S)-1-(4-chloro-2-pyridinyl)-3-buten-1-yl]-, 1,1-dimethylethyl ester

Product 1

HCID 68079321tert-Butyl N-[(1S)-1-[4-(2-aminophenyl)pyridin-2-yl]but-3-en-1-yl]carbamateYield 83.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
90 °C

Procedure

45C (2 g, 7.07 mmol) and (2-aminophenyl)boronic acid (1.065 g, 7.78 mmol) in DMSO (35.4 ml) and H2O (0.637 ml, 35.4 mmol) was de-gassed for 30 min. Then, Phosphoric acid, potassium salt (3.00 g, 14.15 mmol) and 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(ii) dichloromethane complex (0.518 g, 0.707 mmol) were added. The dark red reaction mixture was sealed and heated at 90° C. overnight. The reaction mixture was diluted with EtOAc/Ether and washed with water and brine. The organic layer was dried over MgSO4. Filtered and concentrated to give the crude product as a black oil. The residue was purified by silica gel chromatography to give the desired product (2.0 g, 83%) as a light brownish foam. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.61 (d, J=4.8 Hz, 1H), 7.37-7.28 (m, 2H), 7.27-7.16 (m, 2H), 7.12 (d, J=7.7 Hz, 1H), 6.85 (t, J=7.5 Hz, 1H), 6.77 (d, J=7.9 Hz, 1H), 5.79-5.58 (m, 2H), 5.12-4.97 (m, 2H), 4.90-4.80 (m, 1H), 3.80 (br. s., 2H), 2.62 (t, J=6.6 Hz, 2H), 1.44 (s, 9H). MS (ESI) m/z: 340.1 (M+H)+.

Workup

  1. customThe dark red reaction mixture
  2. customwas sealed
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationFiltered
  6. concentrationconcentrated
  7. customto give the crude product as a black oil
  8. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-8d34cf95def047c98f0fd261b62bfe51
Source dataset
uspto-grants-2016_08
Patent number
US09409908B2

Reaction notes

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