Triphenylphosphine → Methyl 3-oxo-3-(4-(4,4,4-trifluorobutoxy)phenyl)propanoate

HRID 1629778Notes

Reaction equation

HRID 1629778 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:14])[CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[F:15][C:16]([F:22])([F:21])[CH2:17][CH2:18][CH2:19]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[O:14]=[C:8]([C:5]1[CH:4]=[CH:3][C:2]([O:1][CH2:19][CH2:18][CH2:17][C:16]([F:22])([F:21])[F:15])=[CH:7][CH:6]=1)[CH2:9][C:10]([O:12][CH3:13])=[O:11]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 1363074,4,4-Trifluorobutan-1-olHCID 508465Methyl (4-Hydroxybenzoyl)acetateHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 86685868Methyl 3-oxo-3-(4-(4,4,4-trifluorobutoxy)phenyl)propanoateYield 80.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 3-(4-hydroxyphenyl)-3-oxopropanoate (7.8 g, 40.2 mmol) and 4,4,4-trifluorobutan-1-ol (5.15 g, 40.2 mmol) in CH2Cl2 (201 mL) at 0° C. was added triphenylphosphine (12.6 g, 48.2 mmol). The mixture was stirred for a few min, and then DIAD (9.37 mL, 48.2 mmol) was added. The reaction was stirred at 0° C. for 30 min, then warmed to rt and stirred for 3 days. The reaction was loaded directly onto a 300 g silica gel column and eluted with EtOAc in hexanes. Fractions containing the product were combined and concentrated to provide Intermediate 14A (9.9 g, 80%) as a colorless solid. 1H NMR (500 MHz, CDCl3) δ 2.03-2.13 (m, 2H), 2.26-2.39 (m, 2H), 3.75 (s, 3H), 3.96 (s, 2H), 4.09 (t, J=6.05 Hz, 2H), 6.92-6.96 (m, 2H), 7.86-7.97 (m, 2H).

Workup

  1. stirringThe reaction was stirred at 0° C. for 30 min
  2. stirringstirred for 3 days
  3. washeluted with EtOAc in hexanes
  4. additionFractions containing the product
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-40c86169cd9a49dfb49c218f4295bcb6
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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