Binap, (A+-)- → HCID 131734950, compound

HRID 921909Notes

Reaction equation

HRID 921909 reaction equation
Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[Si:19]([O:26][CH2:27][CH:28]1[O:33][CH2:32][CH2:31][NH:30][CH2:29]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Si:19]([O:26][CH2:27][CH:28]1[CH2:29][N:30]([C:2]2[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=2)[CH2:31][CH2:32][O:33]1)([C:22]([CH3:25])([CH3:23])[CH3:24])([CH3:21])[CH3:20]

Participants

6

Reactant 3

HCID 634876Binap, (A+-)-HCID 67110015HCID 67110015, compoundHCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate

Product 1

HCID 131734950HCID 131734950, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A round bottom flask was charged with tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (2.020 g, 6.09 mmol), (+/−)-2-(((tert-butyldimethylsilyl)oxy)methyl)morpholine (1.692 g, 7.31 mmol), Pd2(dba)3 (0.558 g, 0.609 mmol) and BINAP (0.379 g, 0.609 mmol) in toluene (20.31 ml). The flask was evacuated and purged with nitrogen (4×) and heated at 100° C. 8 h and cooled to room temperature ON. The reaction mixture was diluted with ethyl acetate and vacuum filtered through a pad of Celite. The filtrate was concentrated in vacuo. The crude residue was purified by column chromatography on the ISCO system (80 g, 0-100% EtOAc/CH2Cl2) to provide (+/−)-tert-butyl (3-(2-(((tert-butyldimethylsilyl)oxy)methyl)morpholino)-2-chloro-5-cyanophenyl)carbamate (1.2321 g) as a yellow solid.

Workup

  1. customThe flask was evacuated
  2. custompurged with nitrogen (4×)
  3. temperature8 h and cooled to room temperature ON
  4. additionThe reaction mixture was diluted with ethyl acetate and vacuum
  5. filtrationfiltered through a pad of Celite
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe crude residue was purified by column chromatography on the ISCO system (80 g, 0-100% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-ede41cc785064f7b8161406f50f365a0
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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