Benzyl Bromide → 2-(Benzyl(tert-butoxycarbonyl)amino)acetic acid

HRID 1595267Notes

Reaction equation

HRID 1595267 reaction equation
[H-].[Na+].[C:3]([NH:10][CH2:11][C:12]([OH:14])=[O:13])([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1>[OH:13][C:12](=[O:14])[CH2:11][N:10]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:3](=[O:4])[O:5][C:6]([CH3:8])([CH3:9])[CH3:7]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 78288N-(tert-butoxycarbonyl)glycine

Product 1

HCID 105158162-(Benzyl(tert-butoxycarbonyl)amino)acetic acidYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold (−20°) suspension of 60% NaH (120 g, 3.00 mol) in THF (700 mL) was added (30 min) a solution of Boc-glycine (175 g, 1.00 mol) in THF (300 mL). Thereafter, benzyl bromide was added to the mixture. After 15 min, the cooling bath was removed. The reaction mixture was stirred at room temperature for 1 h and then heated at reflux for 16 h. The reaction mixture was cooled to 0°. H2O (˜50 mL) was added dropwise over a 30 min period. After another 30 min, H2O (600 mL) was added. The mixture was washed with hexane (3×500 mL). 1N Aqueous HCl (1.3 L) was added slowly to the aqueous layer, followed by the addition of 4N aqueous HCl (300 mL). The aqueous solution was extracted with EtOAc (1.5 L) and then CH2C12 (3×500 mL). The combined organic layers were serially washed with H2O and brine, dried (MgSO4, Na2SO4, charcoal), filtered through diatomaceous earth and concentrated under reduced pressure to give the title compound (241 g, 91% yield) as a pale yellow solid: Mp 94-97°; 1H NMR (400 MHz, DMSO-d6) δ10.5 (broad s, 1H), 7.23-7.33 (m, 5H), 4.40 (s, 2H), 3.80, 3.72 (2s, 2H), 1.38, 1.35 (2s, 9H); MS (FAB) m/z 266 (MH)+; Anal. Calcd for C14H19NO4 (and accounting for water content, 0.58% w/w as determined by Karl Fisher analysis): C, 63.01; H, 7.26; N, 5.25. Found: C, 62.79; H, 7.14; N, 5.13.

Workup

  1. customthe cooling bath was removed
  2. temperatureheated
  3. temperatureat reflux for 16 h
  4. temperatureThe reaction mixture was cooled to 0°
  5. additionH2O (˜50 mL) was added dropwise over a 30 min period
  6. waitAfter another 30 min
  7. additionH2O (600 mL) was added
  8. washThe mixture was washed with hexane (3×500 mL)
  9. addition1N Aqueous HCl (1.3 L) was added slowly to the aqueous layer
  10. additionfollowed by the addition of 4N aqueous HCl (300 mL)
  11. extractionThe aqueous solution was extracted with EtOAc (1.5 L)
  12. washThe combined organic layers were serially washed with H2O and brine
  13. dry with materialdried (MgSO4, Na2SO4, charcoal)
  14. filtrationfiltered through diatomaceous earth
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c57b7e76aa4b41deb77b5888bd4295c4
Source dataset
uspto-grants-2001_09
Patent number
US06288091B1

Reaction notes

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