Pyridine → [(2-Benzyloxy-4-bromo-phenyl)-tert-butoxycarbonylmethyl-amino]-acetic acid tert-butyl ester

HRID 2357127Notes

Reaction equation

HRID 2357127 reaction equation
[C:1]([O:5][C:6](=[O:31])[CH2:7][N:8]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[Br:38]Br>C(Cl)Cl>[C:1]([O:5][C:6](=[O:31])[CH2:7][N:8]([C:17]1[CH:22]=[CH:21][C:20]([Br:38])=[CH:19][C:18]=1[O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 1049PyridineHCID 24408BromineHCID 68637211[(2-Benzyloxy-phenyl)-tert-butoxycarbonylmethyl-amino]-acetic acid tert-butyl ester

Product 1

HCID 90684652[(2-Benzyloxy-4-bromo-phenyl)-tert-butoxycarbonylmethyl-amino]-acetic acid tert-butyl esterYield 79.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a −78° C. solution of [(2-Benzyloxy-phenyl)-tert-butoxycarbonylmethyl-amino]-acetic acid tert-butyl ester (6.3 g, 14.7 mmol) in CH2Cl2 (100 mL) was added pyridine (1.8 mL, 22.1 mmol) followed by bromine (0.91 mL, 17.6 mmol) under an Ar atmosphere. After 30 min, the mixture was allowed to warm to room temperature and then washed with water, 5% sodium bicarbonate, and brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography, eluting with CH2Cl2/hexane/EtOAc=1:4:0.2 to yield 5.9 g (79%) of 13 as a white solid. Rf=0.43 (in CH2Cl2/hexane/EtOAc=1:4:0.2); 1H NMR (300 MHz, CDCl3) δ 7.45-7.26 (m, 5H), 6.99 (m, 2H), 6.73 (m, 1H), 5.09 (s, 2H), 4.04 (s, 4H), 1.41 (s, 18H); 13C NMR (75 MHz, CDCl3) δ 170.1, 151.1, 138.7, 136.6, 128.6, 127.9, 127.4, 124.1, 120.5, 117.6, 113.7, 81.2, 71.2, 54.5, 28.0; mass spectrum, calculated for C25H32BrNO5 (MH+) 506.2, Found 505.8.

Workup

  1. washwashed with water, 5% sodium bicarbonate, and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash column chromatography
  5. washeluting with CH2Cl2/hexane/EtOAc=1:4:0.2

Sources & evidence

ORD record
ord-6b9f08d186df4524a850bf6534c4f7b2
Source dataset
uspto-grants-2010_07
Patent number
US07759459B2

Reaction notes

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