Hydrochloric Acid → HCID 11284867, compound

HRID 1765442Notes

Reaction equation

HRID 1765442 reaction equation
[C:1]([O:5][C:6]([CH:8]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:9]1[CH:20]=[CH:19][C:12]([CH2:13][C@@H:14]([C:16]([OH:18])=[O:17])[NH2:15])=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:28](ON1C(=O)CCC1=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].C([O-])(O)=O.[Na+].Cl>O1CCOCC1.O>[C:28]([NH:15][C@H:14]([C:16]([OH:18])=[O:17])[CH2:13][C:12]1[CH:19]=[CH:20][C:9]([CH:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[CH:10][CH:11]=1)([O:30][CH2:31][CH:32]1[C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:39]2[C:44]1=[CH:43][CH:42]=[CH:41][CH:40]=2)=[O:29]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium BicarbonateHCID 11188144HCID 11188144, compound

Product 1

HCID 11284867HCID 11284867, compoundYield 50.7%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A mixture of 4-(di-tert-butoxycarbonyl-methyl)-L-phenylalanine (818 mg, 2.16 mmol), Fmoc-OSu (727 mg, 2.16 mmol) and NaHCO3 (906 mg, 10.8 mmol, 5 equivalents) in 48 ml of dioxane-water (1:1) was stirred at room temperature overnight. The reaction mixture was then cooled to 0° C. and acidified with 180 ml of 0.2 M HCl. The reaction product was extracted with ethyl acetate (30 ml×3), and the combined organic extracts were washed with brine, dried (Na2SO4) and concentrated. The crude product was purified by silica gel chromatography (CDCl3-EtOAc-MeOH) to provide N-Fmoc-4-(di-tert-butoxycarbonyl-methyl)-L-phenylalanine as a white solid (650 mg, 50.7%). 1H NMR (DCMSO) δ: 12.704 (1H, s, br), 7.786 (2H, d, J=7.32 Hz), 7.760 (1H, d, J=8.54 Hz), 7.658 (2H, t, J=7.81 Hz), 7.435˜7.200 (4H, m) 7.254 (4H, s), 4.586 (1H, s), 4.274˜4.081 (4H, m), 3.111˜3.040 (1H, dd, J=4.40, 13.67 Hz), 2.913˜2.815 (1H, dd, J=10.75, 13.92 Hz), 1.390 (1H, s), 1.380 (1H, s). FABMS (+Ve), m/z 602 [MH+], 546 [MH+—C4H8], 490 [MH+—2 C4H8]. Anal. calcd. for C20H29NO6: C, 66.90; H, 6.5; N, 2.3. Found: C, 90.40; H, 6.67; N, 2.24.

Workup

  1. temperatureThe reaction mixture was then cooled to 0° C.
  2. extractionThe reaction product was extracted with ethyl acetate (30 ml×3)
  3. washthe combined organic extracts were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel chromatography (CDCl3-EtOAc-MeOH)

Sources & evidence

ORD record
ord-46ba433fd04b409f98c960d7a2f26016
Source dataset
uspto-grants-2007_06
Patent number
US07226991B1

Reaction notes

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