Sodium Hydroxide → Diphenyl Ether

HRID 875541Notes

Reaction equation

HRID 875541 reaction equation
[CH:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]([C@@H](O)[C@H](C)CNC(=O)C3C=CC=CC=3)[CH:12]=[CH:13][CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3]C1.O.NN.[OH-].[Na+].CC[O-].[Na+]>>[C:9]1([O:8][C:7]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:1]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 4

HCID 14798Sodium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 2723922Sodium ethoxideHCID 67316167HCID 67316167, compound

Product 1

HCID 7583Diphenyl Ether

Conditions

Temperature
60 °C

Procedure

A mixture of N-((2R,3S)-3-(3-(cyclohexylmethoxy)phenyl)-3-hydroxy-2-methylpropyl)benzamide (0.179 g, 0.47 mmol), hydrazine monohydrate (0.2 mL), aqueous solution of NaOH (50% w/w, 0.5 mL) and NaOEt (30% in MeOH, 1 mL) was heated at 60° C. under argon for 6 days. The reaction mixture was concentrated under reduced pressure, brine added and the product was extracted into MTBE. The mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (5% 7N NH/MeOH in CH2Cl2) to give Example 76 as a colorless oil. Yield (0.049 g, 38%). 1H NMR (400 MHz, DMSO-d6) δ 7.15 (t, J=8.0 Hz, 1H), 6.78-6.81 (m, 2H), 6.88-6.72 (m, 1H), 4.60 (d, J=4.1 Hz, 1H), 3.71 (d, J=6.5 Hz, 2H), 2.56 (dd, J=6.3 Hz, 12.5 Hz, 1H), 2.40 (dd, J=6.1 Hz, 12.5 Hz, 1H), 1.50-1.84 (m, 7H), 1.08-1.27 (m, 4H), 0.96-1.07 (m, 2H), 0.66 (d, J=6.9 Hz, 3H); ESI MS 278.5 [M+H]+. Chiral HPLC: 92.6%, tR=10.0 min.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, brine
  2. additionadded
  3. extractionthe product was extracted into MTBE
  4. concentrationThe mixture was concentrated under reduced pressure
  5. customthe residue was purified by flash chromatography (5% 7N NH/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-15a1865725be457fb2c949a04c7468a6
Source dataset
uspto-grants-2015_03
Patent number
US08981153B2

Reaction notes

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