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

HRID 1945039Notes

Reaction equation

HRID 1945039 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, 9H) 2.48 (A of ABX, Jab=15.9 Hz, Jax=5.6 Hz, 1H) 2.54 (B of ABX, Jab=15.9 Hz, Jbx=5.3 Hz, 1H) 2.72-2.88 (m, 2H) 4.11 (br s, 1H) 5.02 (br s, 1H) 5.10 (A of AB, J=12.1 Hz, 1H) 5.16 (A of AB, J=12.1 Hz, 1H) 7.00 (d, J=8.1 Hz, 2H) 7.34-7.39 (m, 7H).

Workup

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

Sources & evidence

ORD record
ord-dc419522af734411a223b7dcf02ff81a
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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