Potassium Carbonate → HCID 90457512, compound

HRID 625875Notes

Reaction equation

HRID 625875 reaction equation
Br.[NH2:2][C@@H:3]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[C:10]([Br:15])[CH:9]=1)[C:4]([OH:6])=[O:5].[C:16](=[O:19])([O-:18])[O-].[K+].[K+].[C:22](Cl)(=[O:38])[O:23][CH2:24][CH:25]1[C:37]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[C:31]2[C:26]1=[CH:27][CH:28]=[CH:29][CH:30]=2>O1CCOCC1.O>[CH:27]1[C:26]2[CH:25]([CH2:24][O:18][C:16]([NH:2][C@@H:3]([CH2:7][C:8]3[CH:13]=[CH:12][C:11]([O:14][C:22]([O:23][CH2:24][CH:25]4[C:37]5[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=5[C:31]5[C:26]4=[CH:27][CH:28]=[CH:29][CH:30]=5)=[O:38])=[C:10]([Br:15])[CH:9]=3)[C:4]([OH:6])=[O:5])=[O:19])[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31]=2[CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 343679-Fluorenylmethyl chloroformateHCID 118989351HCID 118989351, compound

Product 1

HCID 90457512HCID 90457512, compoundYield 110.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (S)-2-amino-3-(3-bromo-4-hydroxyphenyl)propanoic acid, hydrobromide (3 g, 8.80 mmol) in 1,4-Dioxane (12 mL) and Water (48 mL) was added potassium carbonate (4.86 g, 35.2 mmol) followed by (9H-fluoren-9-yl)methyl carbonochloridate (2.276 g, 8.80 mmol) at 0° C. The mixture was stirred at RT for 18 hrs and then treated with water (50 mL). The resulting mixture was extracted with diethyl ether (2×15 ml). The aqueous phase was acidified with aq. HCl (1M) to pH 2-3, and extracted with DCM (3×20 ml). The combined organic layers were dried over MgSO4 and concentrated to give the crude product. The crude product was purified via silica gel chromatography (120 g column, 30-90% EtOAc:Hexanes, 20 column volumes) to give the product (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-((((9H-fluoren-9-yl)methoxy)carbonyl)oxy)-3-bromophenyl)propanoic acid (3.42 g, 55.2% yield) as a light yellow solid. 1H NMR (400 MHz, chloroform-d) d 7.80 (t, J=7.9 Hz, 4H), 7.68 (d, J=7.6 Hz, 2H), 7.60 (d, J=7.3 Hz, 2H), 7.49-7.32 (m, 9H), 7.16 (br. s., 2H), 5.32 (s, 1H), 4.73 (br. s., 1H), 4.58 (d, J=7.3 Hz, 2H), 4.54-4.34 (m, 2H), 4.24 (t, J=6.6 Hz, 1H), 3.31-3.03 (m, 2H). ESI-MS (+) m/z=721 (M+H2O).

Workup

  1. extractionThe resulting mixture was extracted with diethyl ether (2×15 ml)
  2. extractionextracted with DCM (3×20 ml)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. customto give the crude product
  6. customThe crude product was purified via silica gel chromatography (120 g column, 30-90% EtOAc:Hexanes, 20 column volumes)

Sources & evidence

ORD record
ord-18b18a583510413597ad383a5d21aaa2
Source dataset
uspto-grants-2016_04
Patent number
US09308236B2

Reaction notes

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