HCID 57988817, compound → HCID 57988838, compound

HRID 406917Notes

Reaction equation

HRID 406917 reaction equation
[CH:1]1([C@@H:4]([OH:18])[CH2:5][O:6][C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][C:8]=2[O:16][CH3:17])[CH2:3][CH2:2]1>CCO.[Pd]>[NH2:13][C:10]1[CH:11]=[CH:12][C:7]([O:6][CH2:5][C@@H:4]([CH:1]2[CH2:2][CH2:3]2)[OH:18])=[C:8]([O:16][CH3:17])[CH:9]=1

Participants

4

Reactant 1

HCID 57988817HCID 57988817, compound

Product 1

HCID 57988838HCID 57988838, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a solution of (R)-1-cyclopropyl-2-(2-methoxy-4-nitrophenoxy)ethanol (20.90 g, 83 mmol) in EtOH (546 ml) was added 5% Pd/C, dry basis, Degussa type 50% water content (3.0 g, 0.705 mmol). The suspension was hydrogenated (1 atm. H2, balloon) at 20° C. for 2.5 h; whereupon, LC/MS analysis revealed the reaction to be complete. After filtration of the reaction mixture through Celite pad and subsequent washing of the cake with EtOH, the filtrate was concentrated under vacuum using a rotary evaporator to yield (R)-2-(4-amino-2-methoxyphenoxy)-1-cyclopropylethanol as a brown solid. M.P. 71° C. (18.34 g, 100%). 1H NMR (400 MHz, CDCl3): δ ppm 0.18-0.27 (m, 1H), 0.38-0.43 (m, 1H), 0.45-0.61 (m, 2H), 0.82-0.92 (m, 1H), 3.21 (ddd, J=8.8, 8.8, 2.6 Hz, 1H), 3.80 (s, 3H), 3.86 (dd, J=10.1, 8.8 Hz, 1H), 4.09 (dd, J=10.1, 2.6 Hz, 1H), 6.21 (dd, J=8.3, 2.7 Hz, 1H). 6.29 (d, J=2.7 Hz, 1H), 6.78 (d, J=8.3 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ ppm 151.2, 142.1, 140.8, 118.7, 106.9, 100.5, 76.5, 74.4, 55.7, 12.9, 2.5, 1.6. HPLC: 6.28 min retention time, 98.5% API; ZORBAX® column SB C18 4.6×75 mm; flow rate 2.5 ml/min; Gradient solvent system: from 100% A:0% B to 0% A:100% B for 8 min (Solvent A: 10% MeOH-90% H2O=0.2% H3PO4; Solvent B: 90% MeOH-10% H2O+0.2% H3PO4) Detection at 220 nm. LC/MS: m/e 224.5 (M+H); 4 min gradient.

Workup

  1. dry with materialdry basis, Degussa type 50% water content (3.0 g, 0.705 mmol)
  2. customat 20° C.
  3. customfor 2.5 h
  4. customthe reaction
  5. filtrationAfter filtration of the reaction mixture through Celite pad
  6. washsubsequent washing of the cake with EtOH
  7. concentrationthe filtrate was concentrated under vacuum
  8. customa rotary evaporator

Sources & evidence

ORD record
ord-94cf2f78f5024e4693ddf286b08cface
Source dataset
uspto-grants-2014_06
Patent number
US08754211B2

Reaction notes

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