Lithium Hydroxide → 17-[2-(3-Fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carboxylic acid

HRID 1443506Notes

Reaction equation

HRID 1443506 reaction equation
C([O:3][C:4]([C:6]12[CH2:23][CH:22]1[CH:21]=[CH:20][CH2:19][CH2:18][CH2:17][CH2:16][N:15]([CH3:24])[C:14](=[O:25])[CH:13]1[CH:9]([CH2:10][CH:11]([O:26][C:27]3[C:36]4[C:31](=[C:32]([CH3:39])[C:33]([O:37][CH3:38])=[CH:34][CH:35]=4)[N:30]=[C:29]([C:40]4[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[CH:41]=4)[N:28]=3)[CH2:12]1)[C:8](=[O:47])[NH:7]2)=[O:5])C.[Li+].[OH-]>C1COCC1.CO.O>[F:46][C:42]1[CH:41]=[C:40]([C:29]2[N:28]=[C:27]([O:26][CH:11]3[CH2:10][CH:9]4[CH:13]([C:14](=[O:25])[N:15]([CH3:24])[CH2:16][CH2:17][CH2:18][CH2:19][CH:20]=[CH:21][CH:22]5[C:6]([C:4]([OH:5])=[O:3])([NH:7][C:8]4=[O:47])[CH2:23]5)[CH2:12]3)[C:36]3[C:31](=[C:32]([CH3:39])[C:33]([O:37][CH3:38])=[CH:34][CH:35]=3)[N:30]=2)[CH:45]=[CH:44][CH:43]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 6841130717-[2-(3-Fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carboxylic acid ethyl ester

Product 1

HCID 6841046617-[2-(3-Fluoro-phenyl)-7-methoxy-8-methyl-quinazolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diaza-tricyclo[13.3.0.0*4,6*]octadec-7-ene-4-carboxylic acidYield 82.6%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
50 °C

Procedure

The ethyl ester 158 (460 mg, 0.713 mmol) was dissolved in THF:MeOH:H2O (2:1:1, 100 mL) and LiOH (1M) (7.13 mL mg, 7.13 mmol) was added to the solution. The reaction was heated to 50° C. for 16 hrs. THF and MeOH was then removed by rotary evaporation and the remaining solution was acidified with 20 mL 10% citric acid (aq). The water phase was extracted with CHCl3 (3×50 mL) and the organic phase was washed with brine. The organic phase was dried with Na2SO4, filtered and concentrated by rotary evaporation. The product was obtained as a white solid (0.363 g, 82%), LRMS (M+H) 617.

Workup

  1. customTHF and MeOH was then removed by rotary evaporation
  2. extractionThe water phase was extracted with CHCl3 (3×50 mL)
  3. washthe organic phase was washed with brine
  4. dry with materialThe organic phase was dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-0d5f153ee205420093a8da805e42d81b
Source dataset
uspto-grants-2010_02
Patent number
US07659245B2

Reaction notes

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