3,3-Difluoro-1-((2-methoxy-4-nitrophenoxy)methyl)cyclobutanol → 1-((4-Amino-2-methoxyphenoxy)methyl)-3,3-difluorocyclobutanol

HRID 2040758Notes

Reaction equation

HRID 2040758 reaction equation
[F:1][C:2]1([F:20])[CH2:5][C:4]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][C:10]=2[O:18][CH3:19])([OH:6])[CH2:3]1>CO.[Pd]>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][C:4]2([OH:6])[CH2:5][C:2]([F:20])([F:1])[CH2:3]2)=[C:10]([O:18][CH3:19])[CH:11]=1

Participants

4

Reactant 1

HCID 579888303,3-Difluoro-1-((2-methoxy-4-nitrophenoxy)methyl)cyclobutanol

Product 1

HCID 575406421-((4-Amino-2-methoxyphenoxy)methyl)-3,3-difluorocyclobutanolYield 100%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of 3,3-difluoro-1-((2-methoxy-4-nitrophenoxy)methyl)cyclobutanol (32.0 g, 111 mmol) prepared in Part F and 10% Pd/C (2.0 g, 1.879 mmol) in 700 mL MeOH was stirred under H2 at 50 psi for 1.5 h. After filtration, the filtrate was concentrated to give 1-((4-amino-2-methoxyphenoxy)methyl)-3,3-difluorocyclobutanol (28.9 g, 111 mmol, quantitative yield) as a light purple solid. 1H NMR (400 MHz, CD3OD) δ ppm 6.68 (1H, d, J=8.56 Hz), 6.35 (1H, d, J=2.52 Hz), 6.16 (1H, dd, J=8.31, 2.52 Hz), 4.77 (3H, br. s.), 3.78 (2H, s), 3.68 (3H, s), 2.68-2.82 (2H, m), 2.38-2.56 (2H, m).

Workup

  1. filtrationAfter filtration
  2. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-7c3dc7ecc8644b3e95dbf0bf0e1f21a5
Source dataset
uspto-grants-2013_11
Patent number
US08580959B2

Reaction notes

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