Lithium Hydroxide → 2-(4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

HRID 2067885Notes

Reaction equation

HRID 2067885 reaction equation
[F:1][CH:2]([F:31])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH2:29][OH:30])[C:24]([O:26]CC)=[O:25])=[CH:19][CH:18]=3)=[N:14][CH:15]=2)=[CH:6][CH:5]=1.[Li+].[OH-]>C1COCC1.CO.O.O>[F:31][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[N:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH2:29][OH:30])[C:24]([OH:26])=[O:25])=[CH:19][CH:18]=3)=[N:12][CH:11]=2)=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 68729053Ethyl 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoate

Product 1

HCID 585422202-(4-(5-(4-(Difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of ethyl 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoate 32 (1 mmol) in THF:MeOH:water (3:2:1 v/v) is added 6 N LiOH (3 mmol). The reaction mixture is stirred at rt for 1 h until complete by LC/MS and diluted with water. The aqueous layer is washed with DCM (2×30 mL) and acidified to pH=5 using aqueous 1N HCl. The resulting mixture is extracted with DCM (3×50 mL). The organic layer is separated, dried over Na2SO4 and concentrated to yield a crude product, which upon crystallization from water yield 2-(4-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)phenyl)-3-hydroxypropanoic acid, 26 as off white solid. 1H NMR (400 MHz, d6-DMSO) δ 9.65 (s, 1H), 8.79 (s, 2H), 7.76 (d, J=8.8 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.30 (s, 1H), 7.27 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.4 Hz, 2H), 3.60-3.70 (m, 2H), 3.50-3.58 (m, 2H), 3.20-3.26 (m, 2H). MS (m/z) (M+1)+: 402.1.

Workup

  1. washThe aqueous layer is washed with DCM (2×30 mL)
  2. extractionThe resulting mixture is extracted with DCM (3×50 mL)
  3. customThe organic layer is separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto yield a crude product, which
  7. customupon crystallization from water

Sources & evidence

ORD record
ord-04e2ba6af92640ebb2aa1fbd29dbf009
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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