Triphenylphosphine → HCID 70807891, compound

HRID 2178653Notes

Reaction equation

HRID 2178653 reaction equation
[C:1]([O:5][C:6](=[O:12])[NH:7][C@@H:8]([CH3:11])[CH2:9][OH:10])([CH3:4])([CH3:3])[CH3:2].[F:13][C:14]1[CH:19]=[CH:18][C:17](O)=[C:16]([C:21]([F:24])([F:23])[F:22])[CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[F:13][C:14]1[CH:19]=[CH:18][C:17]([O:10][CH2:9][C@@H:8]([NH:7][C:6](=[O:12])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH3:11])=[C:16]([C:21]([F:22])([F:23])[F:24])[CH:15]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 5186754-Fluoro-2-(trifluoromethyl)phenolHCID 70231031,1-Dimethylethyl N-((1S)-2-hydroxy-1-methylethyl)carbamate

Product 1

HCID 70807891HCID 70807891, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of tert-butyl[(2S)-1-hydroxypropan-2-yl]carbamate (1.07 g, 6.11 mmol), 4-fluoro-2-(trifluoromethyl)phenol (1.10 g, 5.55 mmol) and triphenylphosphine-resin (2.80 g, 8.40 mmol) in tetrahydrofuran (50 mL) was added drop-wise diisopropyl azodicarboxylate (DIAD, 1.37 g, 6.66 mmol). The reaction was allowed to stir at room temperature for 3 days, then filtered and rinsed with ethyl acetate. The combined filtrate was washed with 0.5 N aqueous sodium hydroxide and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification via silica gel chromatography (50% ethyl acetate in heptane) afforded the title compound as a clear yellow oil. Sample contained some residual diisopropyl azodicarboxylate and carried forward without further purification. Yield: 2.52 g, 134%. LCMS m/z 282.0 {[M-(2-methyl-prop-1-ene)]+1}. 1H NMR (400 MHz, CDCl3) δ 1.31 (d, J=6.8 Hz, 3H), 1.45 (s, 9H), 3.98-4.03 (m, 2H), 4.04-4.13 (m, 1H), 6.95 (dd, J=9.2, 4.2 Hz, 1H), 7.16-7.22 (m, 1H), 7.30 (dd, J=8.3, 3.0 Hz, 1H).

Workup

  1. filtrationfiltered
  2. washrinsed with ethyl acetate
  3. washThe combined filtrate was washed with 0.5 N aqueous sodium hydroxide and saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification via silica gel chromatography (50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-7e7e2e17200b4bd5bee04f635154fb07
Source dataset
uspto-grants-2015_06
Patent number
US09067934B2

Reaction notes

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