Acetic Acid → 4-(2-Amino-2-methylpropyl)phenol acetic acid

HRID 1601473Notes

Reaction equation

HRID 1601473 reaction equation
[CH3:1][C:2]([N+:12]([O-])=O)([CH3:11])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[CH3:15][C:16]([OH:18])=[O:17].CCO>[Pd].CO>[C:16]([OH:18])(=[O:17])[CH3:15].[NH2:12][C:2]([CH3:11])([CH3:1])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 702EthanolHCID 128269024-(2-Methyl-2-nitropropyl)phenol

Product 1

HCID 219232504-(2-Amino-2-methylpropyl)phenol acetic acidYield 86%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A one-gallon high-pressure reactor was charged with 4(2-methyl-2-nitropropyl)phenol (120 g, 614 mmol), HOAc (35.2 mL, 614 mol), 5% Palladium on carbon (24 g) wetted with 2B3 EtOH (60 mL), and MeOH (1230 mL). The mixture was heated to 50° C. with agitation (600 rpm), and the reactor was purged with N2 and pressurized to 50 psi with H2. After 15.5 h the reactor was purged with N2, and the cooled mixture was filtered. The filter cake was washed with MeOH and the filtrate was concentrated to 514 g of slurry on a rotary evaporator. To this slurry was added EtOAc (2 L) with vigorous agitation. After stirring for 1 h, the resulting crystals were filtered and washed with a small amount of EtOAc. The product was dried overnight in a 45° C. vacuum oven to yield 118.83 g (86%) of product as small white needles (mp 211-216° C. dec). This material was 99% pure by HPLC analysis, and while another 9.00 g of material was obtained from the mother liquor it was found to be only 88% pure.

Workup

  1. customthe reactor was purged with N2
  2. customAfter 15.5 h the reactor was purged with N2
  3. filtrationthe cooled mixture was filtered
  4. washThe filter cake was washed with MeOH
  5. concentrationthe filtrate was concentrated to 514 g of slurry on a rotary evaporator
  6. additionTo this slurry was added EtOAc (2 L) with vigorous agitation
  7. filtrationthe resulting crystals were filtered
  8. washwashed with a small amount of EtOAc
  9. customThe product was dried overnight in a 45° C. vacuum oven

Sources & evidence

ORD record
ord-408473d0b81f48089a3d13df89c930b8
Source dataset
uspto-grants-1999_11
Patent number
US05977154

Reaction notes

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