2,3,4-Trifluorobenzoic acid → 3,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}benzoic Acid

HRID 1793017Notes

Reaction equation

HRID 1793017 reaction equation
F[C:2]1[C:10]([F:11])=[C:9]([F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:13][C:14]1[CH:20]=[C:19]([C:21]#[C:22][CH2:23][CH2:24][O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[CH:18]=[CH:17][C:15]=1[NH2:16].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>CCOCC.CCCCCC>[F:11][C:10]1[C:2]([NH:16][C:15]2[CH:17]=[CH:18][C:19]([C:21]#[C:22][CH2:23][CH2:24][O:25][CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][O:27]3)=[CH:20][C:14]=2[F:13])=[C:3]([CH:7]=[CH:8][C:9]=1[F:12])[C:4]([OH:6])=[O:5]

Participants

5

Reactant 3

HCID 3029322,3,4-Trifluorobenzoic acidHCID 2733832Lithium HexamethyldisilazideHCID 220256352-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]aniline

Product 1

HCID 220256423,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}benzoic Acid

Reagents, catalysts & solvents 1

HCID 21584099Diethylether hexaneSolvent

Procedure

2,3,4-Trifluorobenzoic acid and 2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]aniline were reacted in the presence of LiHMDS solution by the general procedure of Example 1, Step B. After workup, followed by purification by column chromatography on silica gel (50% EtOAc as eluant), unreacted aniline (26%), followed by 3,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}benzoic acid (31%) were isolated; m.p. (Et2O/hexane) 175–178° C. 1H NMR [400 MHz, (CD3)2SO] δ 13.55 (v br s, 1 H), 9.28 (br s, 1 H), 7.82 (ddd, J=8.2, 6.0, 1.8 Hz, 1 H), 7.25 (dd, J=12.0, 1.7 Hz, 1 H), 7.16–7.08 (m, 2 H), 6.95 (ddd, J=8.8, 8.8, 5.4 Hz, 1 H), 4.66 (t, J=3.4 Hz, 1 H), 3.83–3.70 (m, 2 H), 3.59–3.41 (m, 2H), 2.68 (t, J=6.8 Hz, 1 H), 1.78–1.58 (m, 2 H), 1.53–1.40 (m, 4 H). Anal. calcd. for C22H20F3NO4: C, 63.0; H, 4.8; N, 3.3. Found C, 63.0; H, 4.8; N, 3.5.

Workup

  1. customAfter workup, followed by purification by column chromatography on silica gel (50% EtOAc as eluant), unreacted aniline (26%)
  2. customwere isolated

Sources & evidence

ORD record
ord-17aba261fdd1485b9bacfe6e52bb4f75
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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