Ethyl Acetate → 2-(2-(2-(2-((4-(1-(tert-Butoxycarbonyl)azetidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid

HRID 1779044Notes

Reaction equation

HRID 1779044 reaction equation
O[Li].O.C[O:5][C:6](=[O:44])[CH2:7][C:8]1[CH:43]=[CH:42][CH:41]=[CH:40][C:9]=1[CH2:10][CH2:11][C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]3[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:30]3)=[CH:25][CH:24]=2)[N:13]=1.CCOC(C)=O>C1COCC1.CO.O>[C:36]([O:35][C:33]([N:31]1[CH2:32][CH:29]([C:26]2[CH:25]=[CH:24][C:23]([NH:22][C:14]3[N:13]=[C:12]([CH2:11][CH2:10][C:9]4[CH:40]=[CH:41][CH:42]=[CH:43][C:8]=4[CH2:7][C:6]([OH:44])=[O:5])[C:17]([C:18]([F:19])([F:21])[F:20])=[CH:16][N:15]=3)=[CH:28][CH:27]=2)[CH2:30]1)=[O:34])([CH3:39])([CH3:37])[CH3:38]

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 168937Lithium hydroxide, monohydrate2×HCID 86712687tert-Butyl 3-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate

Product 1

HCID 867126882-(2-(2-(2-((4-(1-(tert-Butoxycarbonyl)azetidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

LiOH.H2O (0.219 g, 9.131 mmol) was added to a solution of tert-butyl 3-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)azetidine-1-carboxylate (A80) (0.521 g, 0.913 mmol) in THF (10 mL), MeOH (1 mL) and water (1 mL) and the resulting mixture stirred at 40° C. for 20 hours. Additional LiOH.H2O (0.087 g, 3.65 mmol) was added and the mixture heated at 40° C. for a further 24 hours. The volatiles were removed in vacuo and the residue was diluted with 10% citric acid solution (20 mL). Aqueous 1 M HCl (ca 0.5 mL) was then added until a pH of 3 was obtained. EtOAc was added, the layers separated and the aqueous phase extracted with EtOAc (3×20 mL). The combined organics were washed with brine, dried (MgSO4), filtered and evaporated in vacuo to give the title compound A81 as a viscous yellow oil (0.500 g, 98%); 1H NMR (300 MHz, d6-DMSO) δ 9.26 (brs, 1H), 8.52 (s, 1H), 7.57 (d, J=8.5 Hz, 2H), 7.32-7.24 (m, 6H), 4.31 (t, J=8.7 Hz, 2H), 3.97-3.68 (m, 5H), 3.08 (m, 4H), 1.48 (s, 9H). LCMS-B: rt 8.649 min; m/z 557 [M+H]+.

Workup

  1. temperaturethe mixture heated at 40° C. for a further 24 hours
  2. customThe volatiles were removed in vacuo
  3. additionthe residue was diluted with 10% citric acid solution (20 mL)
  4. additionAqueous 1 M HCl (ca 0.5 mL) was then added until a pH of 3
  5. customwas obtained
  6. customthe layers separated
  7. extractionthe aqueous phase extracted with EtOAc (3×20 mL)
  8. washThe combined organics were washed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-d85b803b20db46f8a270278245496b9d
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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