Structure of Fmoc-Val-Ala-OH
CAS No.: 150114-97-9
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CAS No. : | 150114-97-9 |
Formula : | C23H26N2O5 |
M.W : | 410.46 |
SMILES Code : | C[C@H](NC([C@@H](NC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O)C(C)C)=O)C(O)=O |
MDL No. : | MFCD28387722 |
InChI Key : | KQZMZNLKVKGMJS-XOBRGWDASA-N |
Pubchem ID : | 11165770 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sodium carbonate; In 1,4-dioxane; water; at 0℃; for 18h; | (a) (R)-2-((R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-methylbuta propanoic acid (20b) HO-Ala-Val-H 20a (350 mg, 1.86 mmol) and Na2C03 (493 mg, 4.65 mmol) were dissolved in distilled H20 (15 ml.) and the mixture was cooled to 0C before dioxane (15 ml.) was added (partial precipitation of the amino acid salt occurred). A solution of Fmoc-CI (504 mg, 1 .95 mmol) in dioxane (15 ml.) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 ml_). The pH was adjusted from 9 to 2 with 1 N HCI and the aqueous layer was subsequently extracted with EtOAc (3x100 ml_). The combined organics were washed with brine (100 ml_), dried with MgS04, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO-Ala-Val- Fmoc 20b (746 mg, 97% yield). LC/MS 2.85 min (ES+) m/z (relative intensity) 410.60 ; 1H- NMR (400 MHz, CDCI3) delta 7.79 (d, J=7.77 Hz, 2H), 7.60(d, J=7.77 Hz, 2H), 7.43(d, J=7.5 Hz, 2H), 7.34 (d, J=7.5 Hz, 2H), 6.30 (bs, 1 H), 5.30 (bs, 1 H), 4.71-7.56 (m, 1 H), 4.54-4.36 (m, 2H), 4.08-3.91 (m, 1 H), 2.21-2.07 (m, 1 H), 1.50 (d, J=l A Hz, 3H), 1.06-0.90 (m, 6H). |
97% | With sodium carbonate; In 1,4-dioxane; water; at 0℃; for 18h; | HO-Ala-Val-H 1 (350 mg, 1.86 mmol) and Na2C03 (493 mg, 4.65 mmol) were dissolved in distilled H20 (15 mL) and the mixture was cooled to 0C before dioxane (15 mL) was added (partial precipitation of the amino acid salt occurred). A solution of Fmoc-CI (504 mg, 1 .95 mmol) in dioxane (15 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 mL). The pH was adjusted from 9 to 2 with 1 N HCI and the aqueous layer was subsequently extracted with EtOAc (3x100 mL). The combined organics were washed with brine (100 mL), dried with MgS04, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO-Ala-Val- Fmoc 2 (746 mg, 97% yield). LC/MS 2.85 min (ES+) m/z (relative intensity) 410.60 ; 1H-NMR (400 MHz, CDCI3) delta 7.79 (d, J=7.77 Hz, 2H), 7.60(d, J=7.77 Hz, 2H), 7.43(d, J=7.5 Hz, 2H), 7.34 (d, J=7.5 Hz, 2H), 6.30 (bs, 1 H), 5.30 (bs, 1 H), 4.71 -7.56 (m, 1 H), 4.54-4.36 (m, 2H), 4.08-3.91 (m, 1 H), 2.21 -2.07 (m, 1 H), 1 .50 (d, J=7.1 Hz, 3H), 1 .06-0.90 (m, 6H). |
97% | With sodium carbonate; In 1,4-dioxane; water; at 0℃; for 18h; | HO-Ala-Val-H 1 (350 mg, 1 .86 mmol) and Na2C03 (493 mg, 4.65 mmol) were dissolved in distilled H20 (15 ml.) and the mixture was cooled to 0C before dioxane (15 ml.) was added (partial precipitation of the amino acid salt occurred). A solution of Fmoc-CI (504 mg, 1.95 mmol) in dioxane (15 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 mL). The pH was adjusted from 9 to 2 with 1 N HCI and the aqueous layer was subsequently extracted with EtOAc (3x100 mL). The combined organics were washed with brine (100 mL), dried with MgS04, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO- Ala-Val-Fmoc 2 (746 mg, 97% yield). LC/MS 2.85 min (ES+) m/z (relative intensity) 410.60 ; 1H-NMR (400 MHz, CDCI3) delta 7.79 (d, J=7.77 Hz, 2H), 7.60(d, J=7.77 Hz, 2H), 7.43(d, J=7.5 Hz, 2H), 7.34 (d, J=7.5 Hz, 2H), 6.30 (bs, 1 H), 5.30 (bs, 1 H), 4.71-7.56 (m, 1 H), 4.54-4.36 (m, 2H), 4.08-3.91 (m, 1 H), 2.21-2.07 (m, 1 H), 1 .50 (d, J=1A Hz, 3H), 1.06-0.90 (m, 6H). |
97% | With sodium carbonate; In 1,4-dioxane; water; at 0℃; for 18h; | HO-Ala-Val-H 20a (350 mg, 1.86 mmol) and Na2CO3 (493 mg, 4.65 mmol) were dissolved in distilled H20 (15 mL) and the mixture was cooled to 0C before dioxane (15mL) was added (partial precipitation of the amino acid salt occurred). A solution of FmocCl (504 mg, 1.95 mmol) in dioxane (15 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 mL). The pHwas adjusted from 9 to 2 with iN HC1 and the aqueous layer was subsequently extracted with EtOAc (3x100 mL). The combined organics were washed with brine (100 mL), dried with MgSO4, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO-Ala-Val-Fmoc 20b (746 mg, 97% yield). LC/MS 2.85 mm (ES+) rn/z (relative intensity) 410.60 ; ?H-NMR (400 MHz, CDC13) oe 7.79 (d, J7.77 Hz,2H), 7.60(d, J=7.77 Hz, 2H), 7.43(d, J=7.5 Hz, 2H), 7.34 (d, J=7.5 Hz, 2H), 6.30 (bs, 1H),5.30 (bs, 1H), 4.71-7.56 (m, 1H), 4.54-4.36 (m, 2H), 4.08-3.91 (m, 1H), 2.21-2.07 (m,1H), 1.50 (d,J=7.1 Hz, 3H), 1.06-0.90 (m, 6H). |
97% | With sodium carbonate; In 1,4-dioxane; water; at 0℃; for 18.16h; | HO-Ala-Val-H 13(350 mg, 1.86 mmol) and Na2CO3 (493 mg, 4.65 mmol) were dissolved indistilled H20 (15 mL) and the mixture was cooled to 0C before dioxane (15 mL) was added(partial precipitation of the amino acid salt occurred). A solution of Fmoc-Cl (504 mg, 1 .95 mmol) in dioxane (15 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 mL). The pH was adjusted from 9 to 2 with IN HCI and the aqueous layer was subsequently extracted with EtOAc (3x100 mL). Thecombined organics were washed with brine (100 mL), dried with MgSO4, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO-Ala-ValFmoc 14 (746 mg, 97% yield). LC/MS 2.85 mm (ES+) m/z (relative intensity) 410.60 ; NMR (400 MHz, CDCI3) 5 7.79 (d, J7.77 Hz, 2H), 7.60(d, J7.77 Hz, 2H), 7.43(d, J7.5 Hz, 2H), 7.34 (d, J=7.5 Hz, 2H), 6.30 (bs, IH), 5.30 (bs, IH), 4.71-7.56 (m, IH), 4.54-4.36 (m,2H), 4.08-3.91 (m, IH), 2.21-2.07 (m, IH), 1.50 (d, J=7.1 Hz, 3H), 1.06-0.90 (m, 6H). |
97% | With sodium carbonate; In 1,4-dioxane; water; at 0℃; for 18h; | HO-Ala-Val-H 13 (350 mg, 1 .86 mmol) and Na2C03 (493 mg, 4.65 mmol) were dissolved in distilled H20 (15 ml.) and the mixture was cooled to 0C before dioxane (15 ml.) was added (partial precipitation of the amino acid salt occurred). A solution of Fmoc-CI (504 mg, 1 .95 mmol) in dioxane (15 ml.) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 ml_). The pH was adjusted from 9 to 2 with 1 N HCI and the aqueous layer was subsequently extracted with EtOAc (3x100 ml_). The combined organics were washed with brine (100 ml_), dried with MgS04, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO-Ala-Val- Fmoc 14 (746 mg, 97% yield). LC/MS 2.85 min (ES+) m/z (relative intensity) 410.60 ; 1 H- NMR (400 MHz, CDCI3) delta 7.79 (d, J=7.77 Hz, 2H), 7.60(d, J=7.77 Hz, 2H), 7.43(d, J=7.5 Hz, 2H), 7.34 (d, J=7.5 Hz, 2H), 6.30 (bs, 1 H), 5.30 (bs, 1 H), 4.71 -7.56 (m, 1 H), 4.54-4.36 (m, 2H), 4.08-3.91 (m, 1 H), 2.21 -2.07 (m, 1 H), 1 .50 (d, J=7.1 Hz, 3H), 1 .06-0.90 (m, 6H). |
97% | With sodium carbonate; In 1,4-dioxane; water; at 0℃; for 18.16h; | HO-Ala-Val-H 13(350 mg, 1.86 mmol) and Na2CO3 (493 mg, 4.65 mmol) were dissolved indistilled H20 (15 mL) and the mixture was cooled to 0C before dioxane (15 mL) was added(partial precipitation of the amino acid salt occurred). A solution of Fmoc-Cl (504 mg, 1 .95 mmol) in dioxane (15 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 mL). The pH was adjusted from 9 to 2 with IN HCI and the aqueous layer was subsequently extracted with EtOAc (3x100 mL). Thecombined organics were washed with brine (100 mL), dried with MgSO4, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO-Ala-ValFmoc 14 (746 mg, 97% yield). LC/MS 2.85 mm (ES+) m/z (relative intensity) 410.60 ; NMR (400 MHz, CDCI3) 5 7.79 (d, J7.77 Hz, 2H), 7.60(d, J7.77 Hz, 2H), 7.43(d, J7.5 Hz, 2H), 7.34 (d, J=7.5 Hz, 2H), 6.30 (bs, IH), 5.30 (bs, IH), 4.71-7.56 (m, IH), 4.54-4.36 (m,2H), 4.08-3.91 (m, IH), 2.21-2.07 (m, IH), 1.50 (d, J=7.1 Hz, 3H), 1.06-0.90 (m, 6H). |
97% | With sodium carbonate; In 1,4-dioxane; water; at 0℃; for 18.16h; | HO-Ala-Val-H 13(350 mg, 1.86 mmol) and Na2CO3 (493 mg, 4.65 mmol) were dissolved indistilled H20 (15 mL) and the mixture was cooled to 0C before dioxane (15 mL) was added(partial precipitation of the amino acid salt occurred). A solution of Fmoc-Cl (504 mg, 1 .95 mmol) in dioxane (15 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 mL). The pH was adjusted from 9 to 2 with IN HCI and the aqueous layer was subsequently extracted with EtOAc (3x100 mL). Thecombined organics were washed with brine (100 mL), dried with MgSO4, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO-Ala-ValFmoc 14 (746 mg, 97% yield). LC/MS 2.85 mm (ES+) m/z (relative intensity) 410.60 ; NMR (400 MHz, CDCI3) 5 7.79 (d, J7.77 Hz, 2H), 7.60(d, J7.77 Hz, 2H), 7.43(d, J7.5 Hz, 2H), 7.34 (d, J=7.5 Hz, 2H), 6.30 (bs, IH), 5.30 (bs, IH), 4.71-7.56 (m, IH), 4.54-4.36 (m,2H), 4.08-3.91 (m, IH), 2.21-2.07 (m, IH), 1.50 (d, J=7.1 Hz, 3H), 1.06-0.90 (m, 6H). |
97% | HO-Ala-Val-H 20a (350 mg, 1.86 mmol) and Na2C03 (493 mg, 4.65 mmol) were dissolved in distilled H20 (15 niL) and the mixture was cooled to 0C before dioxane (15 mL) was added (partial precipitation of the amino acid salt occurred). A solution of Fmoc-Cl (504 mg, 1.95 mmol) in dioxane (15 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 mL). The pH was adjusted from 9 to 2 with IN HC1 and the aqueous layer was subsequently extracted with EtOAc (3x100 mL). The combined organics were washed with brine (100 mL), dried with MgS04, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO-Ala-Val-Fmoc 20b (746 mg, 97% yield). LC/MS 2.85 min (ES+) m/z (relative intensity) 410.60 ; 1H-NMR (400 MHz, CDC13) delta 7.79 (d, .7=7.77 Hz, 2H), 7.60(d, .7=7.77 Hz, 2H), 7.43(d, .7=7.5 Hz, 2H), 7.34 (d, .7=7.5 Hz, 2H), 6.30 (bs, IH), 5.30 (bs, IH), 4.71-7.56 (m, IH), 4.54-4.36 (m, 2H), 4.08-3.91 (m, IH), 2.21- 2.07 (m, IH), 1.50 (d, .7=7.1 Hz, 3H), 1.06-0.90 (m, 6H). | |
97% | With sodium carbonate; In 1,4-dioxane; water; at 0℃; for 2.16667h; | (a) (R)-2-((R)-2-((((9H-fluoren-9-yI)methoxy)carbonyl)amino)-3-methylbutanamido) propanoic acid (20b)HO-Ala-Val-H 20a (350 mg, 1.86 mmol) and Na2003 (493 mg, 4.65 mmol) were dissolved in distilled H20 (15 mL) and the mixture was cooled to 0C before dioxane (15 mL) was added (partial precipitation of the amino acid salt occurred). A solution of Fmoc-Cl (504 mg, 1.95 mmol) in dioxane (15 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and stirring was maintained for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue dissolved in water (150 mL). The pH was adjusted from 9 to 2 with iN HCI and the aqueous layer was subsequently extracted with EtOAc (3x100 mL). The combined organics were washed with brine (100 mL), dried with MgSO4, filtered and the volatiles removed by rotary evaporation under reduced pressure to afford pure HO-Ala-ValFmoc 20b (746 mg, 97% yield). LC/MS 2.85 mm (ES+) m/z (relative intensity) 410.60; NMR (400 MHz, CDCI3) O 7.79 (d, J=7.77 Hz, 2H), 7.60(d, J=7.77 Hz, 2H), 7.43(d, J=7.5 Hz, 2H), 7.34 (d, J=7.5 Hz, 2H), 6.30 (bs, 1H), 5.30 (bs, 1H), 4.71-7.56 (m, 1H), 4.54-4.36 (m, 2H), 4.08-3.91 (m, 1H), 2.21-2.07 (m, 1H), 1.50 (d, J=7.1 Hz, 3H), 1.06-0.90 (m, 6H). |
94% | With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; for 18h; | H-<strong>[1115-74-8]Val-Ala</strong>-OH 11 (1 .0g, 5.313 mmol, 1.0 eq.) and Na2C03 (1 .42 g, 13.282 mmol, 2.5 eq.) were solubilised in distilled H20 (40 mL) and the mixture was cooled to 0C before dioxane (40 mL) was added. Partial precipitation of the amino acid salt occurred. A solution of Fmoc-CI (1.44 g, 5.579 mmol, 1 .05 eq.) dissolved in dioxane (40 mL) was added dropwise with vigorous stirring over 10 minutes. The resulting mixture was stirred at 0C for 2 hours before the ice bath was removed and the stirring maintained for 16 hours. The solvent was evaporated under reduced pressure and the solid remaining dissolved in water (450 mL). The pH was adjusted to 2 with 1 N HCI (25 mL) and the aqueous layer was subsequently extracted with EtOAc (3 x 250 mL). The combined organics were washed with brine (100 mL), dried over MgS04, filtered and the volatiles removed under reduced pressure to afford pure HO-Ala-Val-Fmoc 12 as a white solid (2.06 g, 94%). LC/MS (2.758min (ES+)), m/z: 41 1 .0 [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta 12.47 (br s, 1 H), 8.20 (d, 1 H, J = 6.7 Hz), 7.89 (d, 2H, J = 7.5 Hz), 7.75 (t, 2H, J = 6.8 Hz), 7.43 - 7.38 (m, 3H), 7.34 - 7.30 (m, 2H), 4.31 - 4.16 (m, 4H), 3.88 (dd, 1 H, J = 8.8, 7.2 Hz), 1 .98 (m, 1 H), 1 .26 (d, 3H, J = 7.3 Hz), 0.89 (d, 3H, J = 6.8 Hz), 0.86 (d, 3H, J = 6.8 Hz). |
With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; for 18h; | To a solution of <strong>[1115-74-8]Val-Ala</strong>-OH (1 g, 5.31 mM) in water (40 ml) is added Na2C03(1.42 g, 13.28 mM) and cooled to 0C before dioxane (40 mL) is added. A solution of Fmoc-Cl (1.44 g, 5.58 mM) in dioxane (40 mL) is added dropwise over 10 min at 0C. The reaction mixture is stirred at 0C for 2h, then allowed to stir at RT for 16 h. Dioxane is removed under vacuum, the reaction mixture diluted with water (450 mL), pH is adjusted to 2 using IN HC1 and extracted with EtOAc (3 x 250 mL). The combined organic layers are washed with brine, dried over MgS04, filtered, concentrated under reduced pressure and dried to yield Fmoc- Val- Ala-OH. This product is suspended in dry DCM (25 ml), PABA (0.785 g, 6.38 mM) and EEDQ (1.971 g, 7.97mM) are added. The resulting mixture is treated under Argon with methanol until a clear solution is obtained. The reaction is stirred overnight and filtered. The filtrate is washed with diethyl ether (4x) and dried under high vacum to yield EC 1930 (1.85 g, 68%). 1H NMR (500 MHz, CD3OD): delta 7.79 (d, = 8.0 Hz, 2H), 7.65 (t, = 7.0 Hz, J2= 7.5 Hz, 2H), 7.54 (d, = 8.0 Hz, 2H), 7.38 (t, = 7.5 Hz, J2= 7.5 Hz, 2H), 7.33-7.24 (m, 4H), 4.54 (s, 2H), 4.48 (q, J = 14.0 Hz, J2= 7.0 Hz, 1H), 4.42-4.32 (m, 2H), 4.22 (t, J1=7.0 Hz, J2= 6.5 Hz, 1H), 3.94 (d, Ji= 7.0 Hz, 1H), 2.07 (m, 1H), 1.43 (d, Jl=7.5 Hz, 3H), 0.97 (d, Jl=7.0 Hz, 3H), 0.95 (d, Ji= 7.0 Hz, 3H); LCMS (ESI): (M + H)+= Calculated for C30H33N3O5, 516.24; found 516.24 | |
With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; for 18h; | To a solution of <strong>[1115-74-8]Val-Ala</strong>-OH (1 g, 5.31 mM) in water (40 ml) was added Na2CO3 (1.42 g, 13.28 mM) and cooled to 0C before dioxane (40 mL) was added. A solution of Fmoc-Cl (1.44 g, 5.58 mM) in dioxane (40 mL) was added dropwise over 10 mm at 0C. The reaction mixture was stirred at 0C for 2h. Then the reaction mixture was allowed to stir at RT for 16 h. Dioxanewas removed under vacuum, the reaction mixture diluted with water (450 mL), pH was adjusted to 2 using iN HC1 and extracted with EtOAc (3 x 250 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, concentrated under reduced pressure and dried to yield Fmoc-<strong>[1115-74-8]Val-Ala</strong>-OH. This product was suspended in dry DCM (25 ml), PABA (0.785 g, 6.38 mM) and EEDQ (1.971 g, 7.97mM) were added. The resulting mixture was treated underArgon with methanol until a clear solution was obtained. The reaction was stuffed overnight andfiltered. The filtrate was washed with diethyl ether (4x) and dried under high vacum to yieldEC1930 (1.85 g, 68%). ?H NMR (500 MHz, CD3OD): 5 7.79 (d, J,= 8.0 Hz, 2H), 7.65 (t, J,=7.0 Hz, J2= 7.5 Hz, 2H), 7.54 (d, J,= 8.0 Hz, 2H), 7.38 (t, J,= 7.5 Hz, J2= 7.5 Hz, 2H), 7.33-7.24 (m, 4H), 4.54 (s, 2H), 4.48 (q, J,= 14.0 Hz, J2= 7.0 Hz, 1H), 4.42-4.32 (m, 2H), 4.22 (t,J,= 7.0 Hz, J2= 6.5 Hz, 1H), 3.94 (d, J,= 7.0 Hz, 1H), 2.07 (m, 1H), 1.43 (d, J,= 7.5 Hz, 3H),0.97 (d, J,= 7.0 Hz, 3H), 0.95 (d, J,= 7.0 Hz, 3H); LCMS (ESI): (M + H) = Calculated for C30H33N305, 516.24; found 516.24 | |
With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; for 18h; | To a solution of <strong>[1115-74-8]Val-Ala</strong>-OH (1 g, 5.31 mM) in water (40 ml) was added Na2CO3 (1.42 g, 13.28 mM) and cooled to 0C before dioxane (40 mL) was added. A solution of Fmoc-Cl (1.44 g, 5.58 mM) in dioxane (40 mL) was added dropwise over 10 mm at 0C. The reaction mixture was stirred at 0C for 2h. Then the reaction mixture was allowed to stir at RT for 16 h.Dioxane was removed under vacuum, the reaction mixture diluted with water (450 mL), pH was adjusted to 2 using iN HC1 and extracted with EtOAc (3 x 250 mL). The combined organic layers were washed with brine, dried over Mg504, filtered, concentrated under reduced pressure and dried to yield Fmoc-<strong>[1115-74-8]Val-Ala</strong>-OH. This product was suspended in dry DCM (25 ml), PABA (0.785 g, 6.38 mM) and EEDQ (1.97 1 g, 7.97mM) were added. The resulting mixture was treated under Argon with methanol until a clear solution was obtained. The reaction was stirred overnight and filtered. The filtrate was washed with diethyl ether (4x) and dried under high vacum to yield Compound 48 (1.85 g, 68%). ?H NMR (500 MHz, CD3OD): (57.79 (d, J,= 8.0 Hz, 2H), 7.65 (t, J,= 7.0 Hz, J2= 7.5 Hz, 2H), 7.54 (d, J,= 8.0 Hz, 2H), 7.38 (t, J,= 7.5 Hz, J2=7.5 Hz, 2H), 7.33-7.24 (m, 4H), 4.54 (s, 2H), 4.48 (q, J,= 14.0 Hz, J2= 7.0 Hz, 1H), 4.42-4.32(m, 2H), 4.22 (t, J,= 7.0 Hz, J2= 6.5 Hz, 1H), 3.94 (d, J,= 7.0 Hz, 1H), 2.07 (m, 1H), 1.43 (d,J,= 7.5 Hz, 3H), 0.97 (d, J,= 7.0 Hz, 3H), 0.95 (d, J,= 7.0 Hz, 3H); LCMS (ESI): (M + H) =Calculated for C30H33N305, 516.24; found 516.24. | |
With sodium carbonate; In 1,4-dioxane; water; at 0 - 20℃; for 18h; | To a solution of<strong>[1115-74-8]Val-Ala</strong>-OH (1 g, 5.31 mM) in water (40 ml) was addedNa2C03 (1.42 g, 13.28 mM) and cooled to 0C before dioxane (40 mL) was added. A solutionofFmoc-Cl (1.44 g, 5.58 mM) in dioxane (40 mL) was added dropwise over 10 min at 0C. Thereaction mixture was stirred at 0C for 2h, then allowed to stir at R T for 16 h. Dioxane was20 removed under vacuum, the reaction mixture diluted with water (450 mL), pH was adjusted to 2using 1N HCl and extracted with EtOAc (3 x 250 mL). The combined organic layers arewashed with brine, dried over MgS04, filtered, concentrated under reduced pressure and driedto yield Fmoc-<strong>[1115-74-8]Val-Ala</strong>-OH. This product was suspended in dry DCM (25 ml), PABA (0.785 g,6.38 mM) and EEDQ (1.971 g, 7.97mM) are added. The resulting mixture was treated under25 Argon with methanol until a clear solution was obtained. The reaction was stirred overnight andfiltered. The filtrate was washed with diethyl ether ( 4x) and dried under high vacum to yieldCompound 18 (1.85 g, 68%). 1H NMR (500 MHz, CD30D): J 7.79 (d, h= 8.0 Hz, 2H), 7.65 (t,h= 7.0 Hz, h= 7.5 Hz, 2H), 7.54 (d, h= 8.0 Hz, 2H), 7.38 (t, h= 7.5 Hz, h= 7.5 Hz, 2H), 7.337.24 (m, 4H), 4.54 (s, 2H), 4.48 (q, lF 14.0 Hz, h= 7.0 Hz, 1H), 4.42-4.32 (m, 2H), 4.22 (t,lF 7.0 Hz, h= 6.5 Hz, 1H), 3.94 (d, lF 7.0 Hz, 1H), 2.07 (m, 1H), 1.43 (d, lF 7.5 Hz, 3H),0.97 (d, h= 7.0 Hz, 3H), 0.95 (d, h= 7.0 Hz, 3H); LCMS (ESI): (M + Ht =Calculated forC3oH33N30s, 516.24; found 516.24 |