Water → HCID 9857778, compound

HRID 2099207Notes

Reaction equation

HRID 2099207 reaction equation
[CH3:1][C:2]1([CH3:16])[C:7]2[CH:8]=[C:9](B(O)O)[CH:10]=[CH:11][C:6]=2[NH:5][C:4](=[O:15])[O:3]1.C(=O)([O-])[O-].[Na+].[Na+].[Br-].[Li+].O.CO[CH2:28][CH2:29][O:30][CH3:31]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][C:2]1([CH3:16])[O:3][C:4](=[O:15])[NH:5][C:6]2[CH:11]=[CH:10][C:9]([C:9]3[CH:8]=[C:7]([CH:28]=[C:29]([O:30][CH3:31])[CH:10]=3)[C:6]#[N:5])=[CH:8][C:7]1=2

Participants

8

Reactant 5

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 82050Lithium BromideHCID 10987806(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)boronic acid

Product 1

HCID 9857778HCID 9857778, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of (4,4-dimethyl-1,4-dihydro-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid (4.2 g, 19.0 mmol), 3-cyano-5-methoxybenzyltriflate (5.1 g, 19.0 mmol), tetrakis(triphenylphosphine)-palladium (0) (1.1 g, 0.95 mmol), sodium carbonate (4.0 g, 38.0 mmol), lithium bromide (5 g, 57 mmol) in DME (50 mL), and water (25 mL) under a blanket of nitrogen, was stirred for 15 minutes at 50° C. This solution was then was heated at 85° C. for 1 hour. The reaction mixture was cooled to room temperature and ethyl acetate (100 mL) was added. The organic layers were washed twice with aqueous ammonium chloride (100 mL) and once with brine (100 mL), dried over magnesium sulfate and concentrated. Purification via chromatography (silica gel, 40% ethyl acetate/hexane) gave 3-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-methoxy-benzonitrile as a white solid (0.69 g, 53%): mp 254-255° C.; 1H-NMR (DMSO-d6) δ 10.4 (s, 1H), 7.84 (s, 1H), 7.67-7.61 (m, 2H), 7.55 (bs, 1H), 7.4 (bs 1H) 6.99 (d, 1H, J=7.94 Hz), 3.88 (s, 3H), 1.67 (s, 6H); MS (EI) m/z 308 ([M+H]+, 30%); Anal. Calcd. For C18H16N2O3: C, 68.13; H, 5.40; N, 8.83. Found: C, 68.03; H, 5.22; N, 8.46.

Workup

  1. temperatureThis solution was then was heated at 85° C. for 1 hour
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washThe organic layers were washed twice with aqueous ammonium chloride (100 mL) and once with brine (100 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customPurification via chromatography (silica gel, 40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-59f971a9661d45ed979f6bb3819341de
Source dataset
uspto-grants-2009_08
Patent number
US07569564B2

Reaction notes

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