Hydrochloric Acid → HCID 11236317, compound

HRID 1640367Notes

Reaction equation

HRID 1640367 reaction equation
[NH:1]([C:16]([O:18][C:19]([CH3:22])(C)C)=[O:17])[C@@H:2]([C:13]([OH:15])=[O:14])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([Cl:12])[CH:5]=1.Cl.[CH:24]1[C:36]2C(COC(ON3C(=O)CCC3=O)=O)[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:28]=2[CH:27]=[CH:26][CH:25]=1.CCOC(C)=O>O1CCOCC1.O>[NH:1]([C:16]([O:18][CH2:19][CH:22]1[C:27]2[C:28](=[CH:36][CH:24]=[CH:25][CH:26]=2)[C:29]2[C:34]1=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:17])[C@@H:2]([C:13]([OH:15])=[O:14])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([Cl:12])[CH:5]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 11809660HCID 11809660, compound

Product 1

HCID 11236317HCID 11236317, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
23 °C

Procedure

Boc-3-Cl-D-Tyr(Me)-OH (9.60 g, 29.1 mmol) was treated with 4 M HCl in dioxane (25 mL) at 23° C. for 1 h then the reaction mixture was concentrated in vacuo. The residual white solid was dissolved in 10% aqueous Na2CO3 (60 mL), dioxane (60 mL) and N-(9-Fluorenylmethoxy-carbonyloxy)succinimide (9.82 g, 29.1 mmol) were added. The reaction mixture was stirred at 23° C. for 18 h, then diluted with water (100 mL). The aqueous phase was extracted with Et2O (2×100 mL), acidified to pH 2 (conc. HCl) and extracted with EtOAc (3×100 mL). The combined EtOAc phases were washed with saturated aqueous NaCl, dried with MgSO4, filtered and concentrated. Without further purification the title compound 8 (12.65 g, 96%) was obtained as white foam. TLC Rf=0.26 (EtOAc, PMA stain); 1H NMR (CDCl3, 400 MHz) δ 9.82 (br s, 1H), 7.76 (d, J=7.6, 2H), 7.56 (t, J=7.6, 2H), 7.39 (t, J=7.6, 2H), 7.31 (d, J=7.6, 2H), 7.19 (d, J=1.6, 1H), 6.99 (dd, J=8.3, 1.6, 1H), 6.80 (d, J=8.3, 1H), 5.44 (d, J=7.8, 1H), 4.64-4.69 (m, 1H), 4.46 (dd, J=10.5, 7.0, 1H), 4.35 (dd, J=10.5, 7.0, 1H), 4.21 (t, J=7.0, 1H), 3.83 (s, 3H), 3.14 (dd, J=14.1, 5.3, 1H), 3.02 (dd, J=14.1, 6.3, 1H); 13C NMR (CDCl3, 101 MHz) δ 175.0, 155.9, 154.2, 143.7, 141.4, 131.1, 128.8, 128.8, 127.8, 127.2, 125.2, 125.1, 120.1, 112.2, 67.2, 56.1, 54.6, 47.2, 36.8; MS (ESI+) m/z 474.1 [M+Na]+ (C25H22ClNNaO5 requires 474.1).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. dissolutionThe residual white solid was dissolved in 10% aqueous Na2CO3 (60 mL)
  3. extractionThe aqueous phase was extracted with Et2O (2×100 mL)
  4. extractionextracted with EtOAc (3×100 mL)
  5. washThe combined EtOAc phases were washed with saturated aqueous NaCl
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customWithout further purification the title compound 8 (12.65 g, 96%)
  10. customwas obtained as white foam

Sources & evidence

ORD record
ord-4f1476c8ce3e4ebc92a7e66661e8f958
Source dataset
uspto-grants-2012_02
Patent number
US08114640B2

Reaction notes

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