Toluene → {4-[4-(2-Benzyloxycarbonylaminoethoxy)phenyl]butyl}carbamic acid tert-butyl ester

HRID 81329Notes

Reaction equation

HRID 81329 reaction equation
[C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:26]([O:33][C:34](=[O:39])[NH:35][CH2:36][CH2:37]Br)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C1(C)C=CC=CC=1>CN(C=O)C>[C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:18][CH2:37][CH2:36][NH:35][C:34]([O:33][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:39])=[CH:16][CH:17]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonate2×HCID 278694benzyl N-(2-bromoethyl)carbamate2×HCID 22592408tert-Butyl [4-(4-hydroxyphenyl)butyl]carbamate

Product 1

HCID 67365450{4-[4-(2-Benzyloxycarbonylaminoethoxy)phenyl]butyl}carbamic acid tert-butyl esterYield 97.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
63 °C

Procedure

[4-(4-Hydroxyphenyl)butyl]carbamic acid tert-butyl ester (38 g, 0.143 mole), cesium carbonate (84 g, 0.257 mole), and (2-bromoethyl)carbamic acid benzyl ester 14 (59 g, 0.23 mole) were combined in DMF (200 ml). The mixture was mechanically stirred under nitrogen at 63° C. for 5.5 h, and allowed to stand at room temperature overnight. An additional amount of (2-bromoethyl)carbamic acid benzyl ester 14 (5 g, 0.019 mole) and cesium carbonate (7.1 g, 0.21 mole) were added, and the reaction was further stirred at 65° C. for 1 h. Toluene was then added, and the stirring mixture was allowed to cool to room temperature. The mixture was suction filtered through a medium sintered glass buchner funnel and washed with toluene. The solvents were removed under vacuum at 75° C. The remaining oil was washed with hexanes (2×400 mL), then dissolved in ether (500 ml) and washed with a mixture of water and brine (10:1, 4×100 mL). The remaining solution was suction filtered through a 30 g pad of silica gel and the solvent evaporated. The residue was washed with hexanes (3×400 ml), and then placed under vacuum for 2 h to afford 61.8 g of the product 15 which was used without further purification. 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9H), 1.54 (m, 4H), 2.56 (t, 2H), 3.20 (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. waitto stand at room temperature overnight
  2. stirringthe reaction was further stirred at 65° C. for 1 h
  3. temperatureto cool to room temperature
  4. filtrationfiltered through a medium sintered glass buchner funnel
  5. washwashed with toluene
  6. customThe solvents were removed under vacuum at 75° C
  7. washThe remaining oil was washed with hexanes (2×400 mL)
  8. dissolutiondissolved in ether (500 ml)
  9. washwashed with a mixture of water and brine (10:1, 4×100 mL)
  10. filtrationfiltered through a 30 g pad of silica gel
  11. customthe solvent evaporated
  12. washThe residue was washed with hexanes (3×400 ml)
  13. waitplaced under vacuum for 2 h

Sources & evidence

ORD record
ord-3de7738ecab64a2dbfe018f904b4726a
Source dataset
uspto-grants-2014_09
Patent number
US08846688B2

Reaction notes

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