Hydrochloric Acid → 7-[2-(Cyclopropylmethoxy)-6-hydroxyphenyl]-1,4-dihydro-5-[(3S)-3-piperidinyl]-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochloride

HRID 2223169Notes

Reaction equation

HRID 2223169 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([O:12]CC3C=CC(OC)=CC=3)[C:7]=2[C:22]2[CH:23]=[C:24]([C@@H:33]3[CH2:38][CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34]3)[C:25]3[CH2:30][O:29][C:28](=[O:31])[NH:27][C:26]=3[N:32]=2)[CH2:3][CH2:2]1.[ClH:46]>O1CCOCC1>[ClH:46].[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([OH:12])[C:7]=2[C:22]2[CH:23]=[C:24]([C@@H:33]3[CH2:38][CH2:37][CH2:36][NH:35][CH2:34]3)[C:25]3[CH2:30][O:29][C:28](=[O:31])[NH:27][C:26]=3[N:32]=2)[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 597146831,1-Dimethylethyl (3S)-3-[7-[2-(cyclopropylmethoxy)-6-[(4-methoxyphenyl)methoxy]phenyl]-1,4-dihydro-2-oxo-2H-pyrido[2,3-d][1,3]oxazin-5-yl]-1-piperidinecarboxylate

Product 1

HCID 1354549037-[2-(Cyclopropylmethoxy)-6-hydroxyphenyl]-1,4-dihydro-5-[(3S)-3-piperidinyl]-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochlorideYield 71%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of tert-butyl (3S)-(−)-3-(7-{2-(cyclopropylmethoxy)-6-[(4-methoxy-benzyl)oxy]phenyl}-2-oxo-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-5-yl)-1-piperidinecarboxylate (1.0 g, 1.624 mmol) in dioxane (15 mL) was added 4N HCl in dioxane (30 mL) at room temperature. The stirring was continued for 3 hrs. After the solvent was removed by evaporation, the resulting solid was triturated with acetonitril, collected by filtration, and washed with acetonitrile. The solid was recrystallized from methanol to give (−)-7-[2-(cyclopropylmethoxy)-6-hydroxy-phenyl]-5-[(3S)-3-piperidinyl]-1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochloride as a white solid (0.502 g, yield; 71%). The absolute configuration for the chiral atom was determined with (S) by the X-ray analysis.

Workup

  1. customAfter the solvent was removed by evaporation
  2. customthe resulting solid was triturated with acetonitril
  3. filtrationcollected by filtration
  4. washwashed with acetonitrile
  5. customThe solid was recrystallized from methanol

Sources & evidence

ORD record
ord-b00d5aab5a9f4890930d7d0c431a5e3b
Source dataset
uspto-grants-2008_05
Patent number
US07375103B2

Reaction notes

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