Phenol → HCID 19627217, compound

HRID 2105306Notes

Reaction equation

HRID 2105306 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[F:11].C([O-])([O-])=O.[K+].[K+].[C:18]1([OH:24])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CN1C(=O)CCC1>C(OCC)(=O)C>[F:11][C:3]1[CH:4]=[C:5]([NH2:8])[CH:6]=[CH:7][C:2]=1[O:24][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 1230531,2-Difluoro-4-nitrobenzene

Product 1

HCID 19627217HCID 19627217, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

1,2-difluoro-4-nitro-benzene Compound 132a (1.3 g, 8.2 mmol), K2CO3 (1.2 g, 9.0 mmol) and phenol Compound 132b (0.84 g, 9.0 mmol.) were combined with 10 mL of NMP in a sealed pressure tube. The reaction was heated in a microwave at 140° C. for 50 min. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over NaSO4, then filtered and concentrated down to an oil. The crude oil in ethyl acetate (25 mL) was added to 10% Pd/C (1.3 g) and placed under 40 psi of hydrogen in a Parr apparatus for 1 hr. The solution was then filtered through Celite and concentrated to give 3-fluoro-4-phenoxy-phenylamine Compound 132c (1.9 g). MS 204 (MH+). An alternative procedure for making Compound 132c is described in U.S. Pat. No. 3,652,665. Using the procedure of Example 1, 3-fluoro-4-phenoxy-phenylamine Compound 132c was used in place of Compound 1e to prepare 4-chloro-6-(3-fluoro-4-phenoxy-phenylamino)-pyrimidine-5-carbonitrile Compound 132d. Using the procedure of Example 1, Compound 132d was carried forward in place of 4-chloro-6-(3-chloro-4-fluoro-phenylamino)-pyrimidine-5-carbonitrile Compound 1f to prepare 5-(3-fluoro-4-phenoxy-phenyl)-4-oxo-4,5-dihydro-3H-1-thia-3,5,6,8-tetraaza-acenaphthylene-2-carboxylic acid Compound 112. MS 423 (MH+). Compound 112 was carried forward in place of Compound 1 and 4-morpholin-4-ylmethyl-phenylamine Compound 3e was used in place of 4-piperidin-1-ylmethyl-phenylamine Compound 1k to give Compound 113. MS 597 (MH+).

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic layer was dried over NaSO4
  3. filtrationfiltered
  4. concentrationconcentrated down to an oil
  5. additionThe crude oil in ethyl acetate (25 mL) was added to 10% Pd/C (1.3 g)
  6. filtrationThe solution was then filtered through Celite
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-149b143dec52442f942fc1560199a9aa
Source dataset
uspto-grants-2009_08
Patent number
US07579356B2

Reaction notes

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