3-Fluorophenol → HCID 54674812, compound

HRID 2402753Notes

Reaction equation

HRID 2402753 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[N:8]=[C:7]([N:9]2[CH2:13][C@@H:12]3[C@H:14]([OH:17])[CH2:15][CH2:16][C@@H:11]3[CH2:10]2)[CH:6]=[CH:5][CH:4]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:39][C:40]1[CH:41]=[C:42](O)[CH:43]=[CH:44][CH:45]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[F:39][C:40]1[CH:45]=[C:44]([CH:43]=[CH:42][CH:41]=1)[O:17][C@@H:14]1[C@@H:12]2[C@@H:11]([CH2:10][N:9]([C:7]3[CH:6]=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:18])[F:19])[N:8]=3)[CH2:13]2)[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 97433-FluorophenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 54674495HCID 54674495, compound

Product 1

HCID 54674812HCID 54674812, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To (3aR,4R,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-ol (90 mg, 0.331 mmol) from Example 30 and triphenylphosphine (173 mg, 0.661 mmol) was added tetrahydrofuran (1.150 mL) and 3-fluorophenol (0.059 mL, 0.661 mmol) followed by dropwise addition of diisopropyl azodicarboxylate (DIAD, 0.129 mL, 0.661 mmol). The reaction mixture was stirred for 7 hours and then quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic washes were purified by silica gel chromatography using 0-6% ethyl acetate/hexane as eluent to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 7.56 (d, J=8.0, 1H), 7.31 (dd, J=15.3, 8.2, 1H), 7.02 (d, J=7.3, 1H), 6.92 (dt, J=11.2, 2.4, 1H), 6.89-6.77 (m, 2H), 6.56 (d, J=8.6, 1H), 4.65 (d, J=2.2, 1H), 3.69 (dd, J=11.0, 8.9, 1H), 3.52 (dd, J=10.7, 7.6, 1H), 3.41 (dd, J=11.3, 4.7, 1H), 3.25 (dd, J=10.7, 3.0, 1H), 2.93-2.78 (m, 2H), 2.10-1.94 (m, 2H), 1.82 (dt, J=13.8, 7.1, 1H), 1.50-1.37 (m, 1H); MS (ESI+) m/z 367 (M+H)+.

Workup

  1. customquenched with saturated aqueous ammonium chloride solution
  2. extractionextracted with ethyl acetate
  3. customThe combined organic washes were purified by silica gel chromatography

Sources & evidence

ORD record
ord-8259368bfb984c5a9aa3d00428d70f30
Source dataset
uspto-grants-2014_08
Patent number
US08796470B2

Reaction notes

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