Hydrochloric Acid → HCID 57947499, compound

HRID 340990Notes

Reaction equation

HRID 340990 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]=2F)=[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.[ClH:48]>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:48])=[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 57947633HCID 57947633, compound

Product 1

HCID 57947499HCID 57947499, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the crude (2S,4R)-5-(di-tert-butoxyphosphoryloxy)-2-(3-(2,3-difluorobenzyl)-1-methylureido)-4-hydroxypentyl isoquinolin-3-ylcarbamate in MeOH (15 mL) at 0° C. was added conc. HCl (12 N, 16 mL, 192.4 mmol) 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 and dried under high vacuum to give (2S,4R)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-hydroxy-5-(phosphonooxy)pentyl isoquinolin-3-ylcarbamate (2.85 g) as a white powder (4.95 g, 89% for 2 steps). LRMS (M−H+) m/z 567.5

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. customdried under high vacuum

Sources & evidence

ORD record
ord-6beae7bba738479aa1d30d79dcfc2055
Source dataset
uspto-grants-2014_11
Patent number
US08895582B2

Reaction notes

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