Tetrahydrofurane dichloromethane → 4-[4-(2-Aminoethoxy)phenyl]-butylcarbamic acid tert-butyl ester

HRID 81330Notes

Reaction equation

HRID 81330 reaction equation
[C:1]([O:5][C:6](=[O:32])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][NH:21]C(OCC2C=CC=CC=2)=O)=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].[H][H].C(Cl)Cl.C1COCC1>C(O)C.[Pd]>[C:1]([O:5][C:6](=[O:32])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH2:20][NH2:21])=[CH:16][CH:17]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 21919333Tetrahydrofurane dichloromethaneHCID 67365450{4-[4-(2-Benzyloxycarbonylaminoethoxy)phenyl]butyl}carbamic acid tert-butyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 588097964-[4-(2-Aminoethoxy)phenyl]-butylcarbamic acid tert-butyl esterYield 76.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

{4-[4-(2-Benzyloxycarbonylaminoethoxy)phenyl]butyl}carbamic acid tert-butyl ester 15 (61.8 g) was stirred in ethanol (500 ml) with 10% palladium on carbon (6 g, wet), under one atmosphere of hydrogen. After stirring for more than 6 h, TLC (silica gel, methylene chloride/THF, 20:1) indicated reaction completion. The complete reaction was flushed with nitrogen, and suction filtered through a pad of Celite, and the pad washed with methylene chloride. The residue (41 g) after evaporation of the methylene chloride was applied to an 800 g pad of silica gel, and sequentially eluted with a mixture of THF and methylene chloride (1.4 L, 2:1), and a mixture of methylene chloride, methanol, and concentrated ammonium hydroxide (30:10:1, 2 L). The fraction containing the product was collected. Evaporation afforded the pure product 16 (32.8 g, 74% over 2 steps). 1H NMR (300 MHz, CDCl3) δ 1.44 (s, 9H), 1.50 (br s, 2H), 1.55 (m, 4H), 2.56 (t, 2H), 3.12 (m, 2H), 3.50 (m, 2H), 3.98 (t, 2H), 4.75 (br s, 1H), 5.00 (br s, 1H), 5.09 (s, 2H), 6.80 (d, 2H), 7.06 (d, 2H), 7.34 (m, 5H).

Workup

  1. customreaction completion
  2. customThe complete reaction
  3. customwas flushed with nitrogen, and suction
  4. filtrationfiltered through a pad of Celite
  5. washthe pad washed with methylene chloride
  6. customThe residue (41 g) after evaporation of the methylene chloride
  7. washsequentially eluted with a mixture of THF and methylene chloride (1.4 L, 2:1)
  8. additiona mixture of methylene chloride, methanol, and concentrated ammonium hydroxide (30:10:1, 2 L)
  9. additionThe fraction containing the product
  10. customwas collected
  11. customEvaporation

Sources & evidence

ORD record
ord-2e9e5449ae2742ac9b5a323963e5bb4f
Source dataset
uspto-grants-2014_09
Patent number
US08846688B2

Reaction notes

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