2,6-Lutidine → HCID 89922411, compound

HRID 921910Notes

Reaction equation

HRID 921910 reaction equation
[Si:1]([O:8][CH2:9][CH:10]1[CH2:15][N:14]([C:16]2[C:17]([Cl:32])=[C:18]([NH:24]C(=O)OC(C)(C)C)[CH:19]=[C:20]([C:22]#[N:23])[CH:21]=2)[CH2:13][CH2:12][O:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C(C)=CC=CC=1C.C(=O)(O)[O-].[Na+]>ClCCl>[NH2:24][C:18]1[CH:19]=[C:20]([CH:21]=[C:16]([N:14]2[CH2:13][CH2:12][O:11][CH:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3])[CH2:15]2)[C:17]=1[Cl:32])[C:22]#[N:23]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 516892Sodium BicarbonateHCID 131734950HCID 131734950, compound

Product 1

HCID 89922411HCID 89922411, compoundYield 87.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a round bottom flask charged with (+/−)-tert-butyl (3-(2-(((tert-butyldimethylsilyl)oxy)methyl)morpholino)-2-chloro-5-cyanophenyl)carbamate (1.2321 g, 2.56 mmol) in Dichloromethane (12.78 ml) and cooled to 0° C. was added 2,6-lutidine (0.595 ml, 5.11 mmol). Trimethyl trifluoromethanesulfonate (0.924 ml, 5.11 mmol) was added drop wise over several minutes. The reaction mixture was stirred at 0° C. 2 h and warmed to room temperature ON. The reaction mixture was poured into a separatory funnel containing 1:1 dichloromethane: saturated aqueous sodium bicarbonate. The aqueous layer was extracted with dichloromethane (2×). The combined organics were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by column chromatography on the ISCO system (40 g, 0-50% EtOAc/CH2Cl2). (+/−)-3-Amino-5-(2-(((tert-butyldimethylsilyl)oxy)methyl)morpholino)-4-chlorobenzonitrile (0.860 g) was isolated as a yellow sticky solid.

Workup

  1. temperature2 h and warmed to room temperature ON
  2. additionThe reaction mixture was poured into a separatory funnel
  3. extractionThe aqueous layer was extracted with dichloromethane (2×)
  4. dry with materialThe combined organics were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified by column chromatography on the ISCO system (40 g, 0-50% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-50fe8d3471174e338610549c6173cc4c
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…