Sodium Carbonate → 3-Chloro-N-{[(9H-fluoren-9-yl)methoxy]carbonyl}-L-tyrosine

HRID 553755Notes

Reaction equation

HRID 553755 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[OH:14])[CH2:5][C@@H:6]([C:8]([OH:10])=[O:9])[NH2:7].C(=O)([O-])[O-].[Na+].[Na+].[C:21](ON1C(=O)CCC1=O)([O:23][CH2:24][CH:25]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]2[C:26]1=[CH:27][CH:28]=[CH:29][CH:30]=2)=[O:22]>O1CCOCC1.O.O1CCOCC1>[C:21]([NH:7][C@H:6]([C:8]([OH:10])=[O:9])[CH2:5][C:4]1[CH:11]=[CH:12][C:13]([OH:14])=[C:2]([Cl:1])[CH:3]=1)([O:23][CH2:24][CH:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:32]2[C:37]1=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:22]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 1109923-Chloro-L-tyrosine2×HCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimide

Product 1

HCID 467373993-Chloro-N-{[(9H-fluoren-9-yl)methoxy]carbonyl}-L-tyrosine

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

3-chlorotyrosine* (Aldrich 51,244-3)(113.5 g, 526 mmol) was added to a roundbottom flask equipped with a mechanical stirrer and temperature probe. 3-chlorotyrosine was dissolved in a solution of dioxane:water 2:1 (500 mL). Sodium carbonate (55.8 g, 526 mmol) was added, and the solution cooled to 0° C. in an ice bath. Fmoc-OSu (177.5 g, 526 mmol) was dissolved in dioxane (300 mL) and added in one portion to the solution at 0° C. The reaction was stirred for 5 hours at 0° C. The reaction was allowed to warm to room temperature overnight. The reaction was concentrated until a volume of 100 mL was achieved. 0.5 M potassium hydrogensulfate was added until the pH was 3. The pH was determined using pH paper (0-14) that was placed directly into the mixture. The pH was determined by comparison to the chart included with the pH paper. The solution was extracted with ethyl acetate (3×500 mL). The organic layers were combined and washed with water (500 mL) and brine (500 mL). The organic layer was then washed over sodium sulfate and concentrated to a constant eight (under vacuum) to give Fmoc-3-chlorotyrosine as a light beige solid. (204 g, 95% purity by area)

Workup

  1. customequipped with a mechanical stirrer
  2. additionadded in one portion to the solution at 0° C
  3. temperatureto warm to room temperature overnight
  4. concentrationThe reaction was concentrated until a volume of 100 mL
  5. addition0.5 M potassium hydrogensulfate was added until the pH was 3
  6. extractionThe solution was extracted with ethyl acetate (3×500 mL)
  7. washwashed with water (500 mL) and brine (500 mL)
  8. washThe organic layer was then washed over sodium sulfate
  9. concentrationconcentrated to a constant eight (under vacuum)

Sources & evidence

ORD record
ord-7ca00b58a8a0436f933c6e55df2bc009
Source dataset
uspto-grants-2011_11
Patent number
US08048906B2

Reaction notes

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