Hydrochloric Acid → (2S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoic acid

HRID 39267

Reaction equation

HRID 39267 reaction equation
C([O:5][C:6](=[O:17])[C@H:7]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)[NH2:8])(C)(C)C.C([O-])(O)=O.[Na+].C1C(=O)N([O:30][C:31]([O:33][CH2:34][CH:35]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:41]3[C:36]2=[CH:37][CH:38]=[CH:39][CH:40]=3)=O)C(=O)C1.Cl>O1CCOCC1.O>[CH:46]1[C:47]2[CH:35]([CH2:34][O:33][C:31]([NH:8][C@H:7]([C:6]([OH:5])=[O:17])[CH2:9][C:10]3[CH:11]=[CH:12][C:13]([OH:16])=[CH:14][CH:15]=3)=[O:30])[C:36]3[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:42]=2[CH:43]=[CH:44][CH:45]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium BicarbonateHCID 6950582L-Tyrosine 1,1-dimethylethyl ester

Product 1

HCID 6957986(2S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoic acidYield 114.2%

Reagents, catalysts & solvents 1

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

Procedure

To a stirring suspension of L-tyrosine O-t-butyl ester (1.00 g, 4.21 mmol) and NaHCO3 (354 mg, 4.21 mmol) in 1,4-dioxane/water (1:1, 20 mL) was added 9-fluorenylmethyl-N-succinimidyl carbonate (1.42 g, 4.21 mmol) and the resulting mixture was stirred for 18 hr at room temperature. The solvent was reduced to 10 mL followed by the addition of 50 mL of cold 1N HCl. The product was extracted with ethyl acetate (3×). The organic extracts were washed with H2O and saturated aqueous NaCl then dried over Na2SO4. The solution was then concentrated after filtration to give the colourless solid 83 (1.94 g, 100%) which was used without purification: 1H NMR (400 MHz, CDCl3) δ 1.43 (s, 9H), 2.97-3.06 (m, 2H), 4.21 (bt, J=7.1, 1H), 4.33 (dd, J=7.1, 10.5, 1H), 4.41-4.53 (m, 2H), 5.01 (bs, 1H), 5.30, (d, J=8.2, 1H), 6.73 (d, J=8.5, 2H), 7.00 (d, J=8.5, 2H), 7.31 (t, J=7.5, 2H), 7.40 (t, J=7.5, 2H), 7.57 (dd, J=3.3, 7.3, 2H), 7.76 (d, J=7.5, 2H).

Workup

  1. extractionThe product was extracted with ethyl acetate (3×)
  2. washThe organic extracts were washed with H2O and saturated aqueous NaCl
  3. dry with materialthen dried over Na2SO4
  4. concentrationThe solution was then concentrated
  5. filtrationafter filtration

Sources & evidence

ORD record
ord-ddd0366ddea54e6589c73b50d84504c8
Source dataset
uspto-grants-2013_09
Patent number
US08524691B2

Linked notes

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