Dimethylformamide → (S)-3-(4-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)phenyl)-2-((tert-butoxycarbonyl)amino)propanoic acid

HRID 611472Notes

Reaction equation

HRID 611472 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].C(N(CC)CC)C.[C:28](C1CC(=O)N(O)C1=O)([O:30][CH2:31][CH:32]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]2[C:33]1=[CH:34][CH:35]=[CH:36][CH:37]=2)=[O:29].CN(C=O)C>ClCCl>[CH3:6][C:4]([CH3:5])([O:3][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:28]([O:30][CH2:31][CH:32]2[C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][C:38]=3[C:39]3[C:44]2=[CH:43][CH:42]=[CH:41][CH:40]=3)=[O:29])=[CH:15][CH:16]=1)=[O:2])[CH3:7]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 2761482(2S)-3-(4-aminophenyl)-2-{[(tert-butoxy)carbonyl]amino}propanoic acidHCID 21653429Fmoc-N-hydroxysuccinimide

Product 1

HCID 2755959(S)-3-(4-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)phenyl)-2-((tert-butoxycarbonyl)amino)propanoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Boc-para-aminophenylalanine (2.6 mmol; 0.72 g) was dissolved in 12 ml of dichloromethane (DCM) (from Dow Chemical, Midland, Mich.) containing 3.85 mmol of triethylamine (TEA) (from Aldrich, Milwaukee, Wis.; distilled before use). 1.3 Grams (3.85 mmol) of Fmoc-N-hydroxysuccinimide was added and the solution was left at room temperature for 10 hours. The solution was evaporated to dryness in vacuo. The residue was dissolved in 100 ml ethyl acetate and washed with 50 ml of 5% NaHCO3. The solution was filtered and the NaHCO3 wash was repeated two more times. The precipitate from the three NaHCO3 washes was then extracted with a mixture of three parts (v/v) ethyl acetate to one part saturated KHSO4. The organic layer was isolated and concentrated in vacuo. After removal of most of the ethyl acetate by vacuum the product was precipitated with petroleum ether. The product was recrystallized twice using an ethyl acetate-petroleum ether mixture to yield 0.83 g (64%) with a melting point of 118-120° C. Thin layer chromatography was performed according to well-known procedures and displayed a spot with Rf=0.28. [α]D21 =-6.29 (c1.7, DMF).

Workup

  1. customThe solution was evaporated to dryness in vacuo
  2. dissolutionThe residue was dissolved in 100 ml ethyl acetate
  3. washwashed with 50 ml of 5% NaHCO3
  4. filtrationThe solution was filtered
  5. washthe NaHCO3 wash
  6. extractionThe precipitate from the three NaHCO3 washes was then extracted with a mixture of three parts (v/v) ethyl acetate to one part saturated KHSO4
  7. customThe organic layer was isolated
  8. concentrationconcentrated in vacuo
  9. customAfter removal of most of the ethyl acetate by vacuum the product
  10. customwas precipitated with petroleum ether
  11. customThe product was recrystallized twice
  12. customto yield 0.83 g (64%) with a melting point of 118-120° C

Sources & evidence

ORD record
ord-757f0cc526c74f0c97291d3d18988bfd
Source dataset
uspto-grants-1999_12
Patent number
US06001810

Reaction notes

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