3-METHYL-4-BROMOACETANILIDE → HCID 58094433, compound

HRID 1034944Notes

Reaction equation

Cl.[CH3:2][C@H:3]1[O:8][CH2:7][CH2:6][NH:5][CH2:4]1.Br[C:10]1[CH:15]=[CH:14][C:13]([NH:16]C(=O)C)=[CH:12][C:11]=1[CH3:20].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>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]>[CH3:20][C:11]1[CH:12]=[C:13]([CH:14]=[CH:15][C:10]=1[N:5]1[CH2:6][CH2:7][O:8][C@H:3]([CH3:2])[CH2:4]1)[NH2:16]

Participants

Conditions

Temperature: 65 °C

Procedure

Under N2 atmosphere, to a mixture of (R)-2-methylmorpholine HCl salt (1.1 g, 8 mmol), N-(4-bromo-3-methylphenyl)acetamide (1.7 g, 7.45 mmol), Pd2 dba3 (92 mg, 0.1 mmol) and 2-(di-t-butylphosphino)biphenyl (72 mg, 0.24 mmol) was added LiHMDS (28 mmol, 28 mL, 1 M in THF). The resulting mixture was stirred at 65° C. overnight. THF was removed under reduced pressure. The residue was treated with HCl (1N), basified with NaHCO3, and then extracted with EtOAc. The combined organics was washed with brine and dried over Na2SO4. The crude was purified by flash chromatography on silica gel (40-100% EtOAc in hexanes) to afford the product as a yellow solid.

Workup

customTHF was removed under reduced pressure
additionThe residue was treated with HCl (1N)
extractionextracted with EtOAc
washThe combined organics was washed with brine
dry with materialdried over Na2SO4
customThe crude was purified by flash chromatography on silica gel (40-100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-d354d4f2305b453e8c1c49e3895092c2
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546370B2

Reaction notes

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