Water → N-Boc-4-(2'-bromoisobutyramido)phenylalanine

HRID 595630Notes

Reaction equation

HRID 595630 reaction equation
[C:1]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Br:21][C:22]([CH3:27])([CH3:26])[C:23](Br)=[O:24].C(Cl)(Cl)Cl.O>C1COCC1>[C:1]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:23](=[O:24])[C:22]([Br:21])([CH3:27])[CH3:26])=[CH:15][CH:16]=1)([O:3][C:4]([CH3:5])([CH3:7])[CH3:6])=[O:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6212ChloroformHCID 886852-Bromo-2-methylpropionyl bromideHCID 2761482(2S)-3-(4-aminophenyl)-2-{[(tert-butoxy)carbonyl]amino}propanoic acid

Product 1

HCID 66691796N-Boc-4-(2'-bromoisobutyramido)phenylalanineYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Commercially available N-Boc 4-aminophenylalanine (3.62 g, 0.01447 mol) was dissolved in 50 mL of dry THF. 2-bromoisobutyryl bromide (1.757 mL, 0.01422 mol) was added dropwise over 30-60 seconds with vigorous stirring. The reaction was complete after 10 min (monitored by TLC). After approximately 20 min. the entire reaction mixture (including newly formed precipitate) was transferred to a separatory funnel with CHCl3, and approximately 100 mL of H2O. The reaction mixture was extracted with CHCl3 (3×50 mL). The organic phase was washed with distilled water (2×50 mL) and brine (50 mL). The organic phase was dried with MgSO4 and evaporated in vacuo to obtain the crude product (4.55 g). The crude solid product was recrystallized in 20-30 mL acetonitrile three times to purify the product. After three recrystallizations, N-Boc-4-(2′-bromoisobutyramido)phenylalanine was obtained in 65% yield (3.63 g). 1H NMR (500 MHz, DMSO): δ9.4 (s, 1H, COOH), δ7.8 (s, 1H, NH), δ7.5 (d, 2H, Ar H), δ7.1 (d, 2H, Ar H), δ6.0 (d, 1H, NH), δ4.2 (d, 1H, CH), δ3.05 (dd, 2H, CH2), δ2.0 (s, 6H, CH3), δ1.3 (s, 9H, CH3).

Workup

  1. customAfter approximately 20 min. the entire reaction mixture (
  2. extractionThe reaction mixture was extracted with CHCl3 (3×50 mL)
  3. washThe organic phase was washed with distilled water (2×50 mL) and brine (50 mL)
  4. dry with materialThe organic phase was dried with MgSO4
  5. customevaporated in vacuo
  6. customto obtain the crude product (4.55 g)
  7. customThe crude solid product was recrystallized in 20-30 mL acetonitrile three times
  8. customto purify the product
  9. customAfter three recrystallizations

Sources & evidence

ORD record
ord-948c2be685fc46eb8fc0763083664b05
Source dataset
uspto-grants-2016_01
Patent number
US09243274B2

Reaction notes

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