Ethanol → ((1S)-5-{3-[[2-chloro-5-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 603496Notes

Reaction equation

HRID 603496 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH3:28])[CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([O:25]CC)=[O:24])[CH2:17][CH2:16]3)[C:5]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)=[CH:4][N:3]=1.C(O)C.O.O[Li].O>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH3:28])[CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([OH:25])=[O:24])[CH2:17][CH2:16]3)[C:5]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 59300424ethyl((1S)-5-{3-[[2-chloro-5-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

Product 1

HCID 59300517((1S)-5-{3-[[2-chloro-5-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetic acidYield 30.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl ((1S)-5-{3-[[2-chloro-5-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (Example 443, 70 mg, 0.137 mmol) in a mixture of THF (2 mL), ethanol (1 mL), and water (2 mL) was added LiOH.H2O (13 mg, 0.55 mmol). The mixture was maintained at rt in an orbital shaker for 16 h after which the reaction mixture was washed with Et2O. To the remaining aqueous solution was added HCl (1N aqueous solution) dropwise until pH 5 was reached. The aqueous solution was then extracted with EtOAc, the combined organic layers dried (Na2SO4), filtered, and concentrated under reduced pressure to give 20 mg (30%) of the product as a white solid. 1H NMR (400 MHz, CDCl3): δ 1.75-1.79 (m, 1H), 2.18-2.21 (m, 2H), 2.24-2.49 (m, 2H), 2.77-2.90 (m, 3H), 3.31 (s, 3H), 3.52-3.74 (m, 1H), 3.92 (s, 3H), 3.99 (t, 2H), 4.05 (t, 2H), 6.67 (d, 1H), 6.75 (s, 1H), 6.94 (d, 2H), 7.08 (s, 1H), 8.15 (s, 1H), 8.27 (d, 2H); LC-MS: RT=2.91 min, (M+H)+ 482.2.

Workup

  1. washwas washed with Et2O
  2. additionTo the remaining aqueous solution was added HCl (1N aqueous solution) dropwise until pH 5
  3. extractionThe aqueous solution was then extracted with EtOAc
  4. dry with materialthe combined organic layers dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2c44089d25164f81a456fe1b0c1901dd
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

Loading…