Benzyl Bromide → (R)-benzyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate

HRID 70862

Reaction equation

HRID 70862 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][C:11]([OH:13])=[O:12])=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+].[CH2:27](Br)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C@@H:9]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][C:11]([O:13][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:12])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 516892Sodium BicarbonateHCID 7009737(3R)-4-(4-bromophenyl)-3-{[(tert-butoxy)carbonyl]amino}butanoic acid

Product 1

HCID 59607538(R)-benzyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoateYield 89.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of (R)-4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoic acid (5.02 g, 14.01 mmol) and NaHCO3 (3.53 g, 42.0 mmol) in DMF (20 mL) is added Benzyl bromide (5.10 mL, 42 mmol) at room temperature under nitrogen. After stirring for 46 hours, the reaction is diluted with H2O (200 mL), and then precipitated solid is collected and washed with H2O (500 mL) and then with heptane (200 ml) to give (R)-benzyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (5.61 g, 89%). HPLC retention time=1.56 minutes (condition B); MS (ES+)=392.1 (m-tBu+2); 348.1 (m-Boc+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.39 (s, 9 H) 2.48 (A of ABX, Jab=15.9 Hz, Jax=5.6 Hz, 1 H) 2.54 (B of ABX, Jab=15.9 Hz, Jbx=5.3 Hz, 1 H) 2.72-2.88 (m, 2 H) 4.11 (br s, 1 H) 5.02 (br s, 1 H) 5.10 (A of AB, J=12.1 Hz, 1 H) 5.16 (A of AB, J=12.1 Hz, 1 H) 7.00 (d, J=8.1 Hz, 2 H) 7.34-7.39 (m, 7 H).

Workup

  1. customprecipitated solid
  2. customis collected
  3. washwashed with H2O (500 mL)

Sources & evidence

ORD record
ord-e2c197c0777549a0a3d1f071437e6529
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Linked notes

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