Hydrochloric Acid → HCID 57947499, compound

HRID 416421Notes

Reaction equation

HRID 416421 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:47])[O:13][CH2:14][C@@H:15]([N:33]([CH3:46])[C:34]([NH:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:39]=2[Cl:45])=[O:35])[CH2:16][C@@H:17]([OH:32])[CH2:18][O:19][P:20]([O:27]C(C)(C)C)([O:22]C(C)(C)C)=[O:21])[N:2]=1.Cl>CO>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12](=[O:47])[O:13][CH2:14][C@@H:15]([N:33]([CH3:46])[C:34]([NH:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[C:39]=2[Cl:45])=[O:35])[CH2:16][C@@H:17]([OH:32])[CH2:18][O:19][P:20]([OH:27])([OH:22])=[O:21])[N:2]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57947763HCID 57947763, compound

Product 1

HCID 57947499HCID 57947499, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the above crude (2S,4R)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(di-tert-butoxyphosphoryloxy)-4-hydroxypentyl isoquinolin-3-ylcarbamate in MeOH (8 mL) at 0° C. was added conc. HCl (12 N, 8 mL, 20 equiv.) dropwise. The mixture was stirred for 30 min and concentrated. The residue was dissolved in 50 mL H2O. Aqueous NaOH solution (1 N) was added to adjusted the PH to 3-4. EtOAc (50 mL) was then added. The mixture was stirred at RT for 1 h. The white solid was then filtered and washed with H2O and EtOAc, followed by drying in vacuo to give (2S,4R)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-hydroxy-5-(phosphonooxy)pentyl isoquinolin-3-ylcarbamate as a white powder (2.4 g, 86% for 2 steps). LRMS (M+H) m/z 585.5.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in 50 mL H2O
  3. additionAqueous NaOH solution (1 N) was added
  4. additionEtOAc (50 mL) was then added
  5. stirringThe mixture was stirred at RT for 1 h
  6. filtrationThe white solid was then filtered
  7. washwashed with H2O and EtOAc
  8. customby drying in vacuo

Sources & evidence

ORD record
ord-9f5077ecb140427993d797c029e193ec
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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