Citric Acid → Fmoc-Ala-Lys(Mtr)

HRID 1883297Notes

Reaction equation

HRID 1883297 reaction equation
[NH:1]([C:14]([O:16][CH2:17][CH:18]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]2[C:19]1=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[C@H:2]([C:4](ON1C(=O)CCC1=O)=[O:5])[CH3:3].[NH2:31][C@H:32]([C:52]([OH:54])=[O:53])[CH2:33][CH2:34][CH2:35][CH2:36][NH:37][S:38]([C:41]1[C:50]([CH3:51])=[C:48]([CH3:49])[C:45]([O:46][CH3:47])=[CH:44][C:42]=1[CH3:43])(=[O:40])=[O:39].C(=O)(O)[O-].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>COCCOC.O.O.COCCOC>[NH:1]([C:14]([O:16][CH2:17][CH:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:25]2[C:30]1=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:15])[C@H:2]([C:4]([NH:31][C@H:32]([C:52]([OH:54])=[O:53])[CH2:33][CH2:34][CH2:35][CH2:36][NH:37][S:38]([C:41]1[C:50]([CH3:51])=[C:48]([CH3:49])[C:45]([O:46][CH3:47])=[CH:44][C:42]=1[CH3:43])(=[O:40])=[O:39])=[O:5])[CH3:3]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 516893Potassium BicarbonateHCID 136701002,5-Dioxopyrrolidin-1-yl N-(((9H-fluoren-9-yl)methoxy)carbonyl)-L-alaninateHCID 15662507Lys(Mtr)

Product 1

HCID 131724483Fmoc-Ala-Lys(Mtr)

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

A solution of Fmoc-Ala-OSu 7c (15.31 mmol) in DME (100 mL) was added to a stirred solution of Lys(Mtr) 2 (6.4080 g, 1 equiv) and potassium bicarbonate (1.5331 mg, 1 equiv) in 2:1 water/DME (150 mL). After 16 h the DME was removed in vacuo and the resulting suspension was treated with citric acid (3.22 g, 1.1 equiv) in water (25 mL). The mixture was extracted with ethyl acetate. The organic phase was washed with water (2×) and brine, dried over sodium sulfate, and concentrated in vacuo, giving a yellow foam which was carried on without further purification. 1H-NMR (CDCl3/CD3OD) δ 1.25 (m, 2H), 1.32 (d, 3H), 1.57 (m, 3H), 1.73 (m, 1H), 2.41 (brt, 2H), 3.72 (s, 3H), 4.14 (m, 1H), 4.29 (m, 4H), 6.79 (d, 2H), 7.22 (m, 16H), 7.38 (d, 4H), 7.52 (m, 2H), 7.72 (d, 2H). MS (FAB) 712.2 (MH)+, 750.2 (M+K)+.

Workup

  1. customAfter 16 h the DME was removed in vacuo
  2. extractionThe mixture was extracted with ethyl acetate
  3. washThe organic phase was washed with water (2×) and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customgiving a yellow foam which
  7. customwas carried on without further purification

Sources & evidence

ORD record
ord-ea81c891f61e4751a4becfdeeef77007
Source dataset
uspto-grants-2004_07
Patent number
US06759509B1

Reaction notes

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