1,4-Dioxane → HCID 59814410, compound

HRID 1908948Notes

Reaction equation

HRID 1908948 reaction equation
Br.[NH2:2][CH:3]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]2[NH:12][C:13]3[C:18]([C:19]=2[CH:20]=1)=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]([OH:6])=[O:5].C(=O)([O-])O.[Na+].O1CCOCC1.Cl[C:33]([O:35][CH2:36][CH:37]1[C:49]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[C:43]2[C:38]1=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:34]>O>[CH:10]1[C:11]2[NH:12][C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:19]=2[CH:20]=[C:8]([CH2:7][CH:3]([NH:2][C:33]([O:35][CH2:36][CH:37]2[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][C:43]=3[C:44]3[C:49]2=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:34])[C:4]([OH:6])=[O:5])[CH:9]=1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 343679-Fluorenylmethyl chloroformateHCID 516892Sodium BicarbonateHCID 131727107HCID 131727107, compound

Product 1

HCID 59814410HCID 59814410, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Crude 2-Amino-3-(9H-carbazol-3-yl)-propionic acid HBr salt (50 mg, 0.15 mmol) was combined with aqueous sodium hydrogen carbonate (2 mL of a saturated solution) and dioxane (2 mL) and stirred at about 0° C. 9-Fluorenylmethyl chloroformate (100 mg, 0.39 mmol) was added and the reaction stirred at room temperature for about 8 h. The reaction mixture was diluted with water (25 mL), and extracted with diethyl ether (2×25 mL). The aqueous layer was acidified with hydrochloric acid to pH 3, and extracted with ethyl acetate (3×25 mL). The combined ethyl acetate extracts were concentrated under reduced pressure and dried in vacuo. The crude product was purified using column chromatography on silica gel with 10% methanol in dichloromethane as eluant to afford rac-3-(9H-Carbazol-3-yl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (ES-MS (M+H)+ 477.2 (calc. 477.17)), which was utilized directly in the synthesis of peptide analogs by solid phase peptide synthesis protocols.

Workup

  1. stirringthe reaction stirred at room temperature for about 8 h
  2. extractionextracted with diethyl ether (2×25 mL)
  3. extractionextracted with ethyl acetate (3×25 mL)
  4. concentrationThe combined ethyl acetate extracts were concentrated under reduced pressure
  5. customdried in vacuo
  6. customThe crude product was purified

Sources & evidence

ORD record
ord-f243060d02cf4c41b6bad395d12e23b9
Source dataset
uspto-grants-2013_12
Patent number
US08598312B2

Reaction notes

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