Methanol → Tert-butyl 3-(4-amino-2-methoxyphenoxy)azetidine-1-carboxylate

HRID 554841Notes

Reaction equation

HRID 554841 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][C:14]=2[O:22][CH3:23])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.C1(C)C=CC=CC=1>C1COCC1.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][C:14]=2[O:22][CH3:23])[CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 887MethanolHCID 1140TolueneHCID 46835555Tert-butyl 3-(2-methoxy-4-nitrophenoxy)azetidine-1-carboxylate

Product 1

HCID 46835556Tert-butyl 3-(4-amino-2-methoxyphenoxy)azetidine-1-carboxylateYield 101%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve 3-(2-methoxy-4-nitro-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (210 g, 639 mmol) in THF (630 mL) and transfer with MeOH (1680 mL) to a stainless steel tank containing 10% palladium on carbon pre-wet with toluene. Hydrogenate the mixture on a Parr shaker for 2.5 h. Remove the catalyst by filtration through diatomaceous earth and rinse the solids with MeOH. Concentrate the filtrate in vacuo, and then co-evaporate the residue three times with heptane (500 mL each time) to obtain 190 g (99%) of the title compound as a tan solid which is used immediately in the next reaction. 1H NMR (300 MHz, CDCl3) δ: 6.48 (d, 1H, J=8.5), 6.30 (d, 1H, J=2.6), 6.17 (dd, 1H, J=2.4, 8.5), 4.77 (m, 1H), 4.19 (m, 2H), 4.04 (m, 2H), 3.81 (s, 3H), 3.59 (br s, 2H), 1.42 (s, 9H).

Workup

  1. customfor 2.5 h
  2. customRemove the catalyst
  3. filtrationby filtration through diatomaceous earth
  4. washrinse the solids with MeOH
  5. concentrationConcentrate the filtrate in vacuo

Sources & evidence

ORD record
ord-1f1907e74ba94f52804d69bf52f5d55a
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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