Lithium Hydroxide → HCID 57516104, compound

HRID 2409186Notes

Reaction equation

HRID 2409186 reaction equation
C([O:3][C:4]([C@@H:6]1[C@@H:11]2[C@H:7]1[CH2:8][C@@H:9]([OH:32])[CH:10]2[NH:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]([C@:20]2([CH3:31])[C:25]([CH3:27])([CH3:26])[C:24](=[O:28])[N:23]([CH3:29])[C:22]([NH2:30])=[N:21]2)[CH:14]=1)=[O:5])C.[Li+].[OH-]>C1COCC1.CO.O>[NH2:30][C:22]1[N:23]([CH3:29])[C:24](=[O:28])[C:25]([CH3:26])([CH3:27])[C@:20]([C:15]2[CH:14]=[C:13]([NH:12][CH:10]3[C@H:9]([OH:32])[CH2:8][C@@H:7]4[C@H:11]3[C@H:6]4[C:4]([OH:5])=[O:3])[CH:18]=[CH:17][C:16]=2[F:19])([CH3:31])[N:21]=1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 66727893HCID 66727893, compound

Product 1

HCID 57516104HCID 57516104, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,3R,5R,6S)-2-[3-((S)-2-Amino-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-4-yl)-4-fluoro-phenylamino]-3-hydroxy-bicyclo[3.1.0]hexane-6-carboxylic acid ethyl ester (example 100, 0.05 mmol) in THF (1 ml), MeOH (0.3 ml) and H2O (0.3 ml) was added LiOH (1N, 0.1 mmol) and the reaction mixture was stirred at room temperature for 4 h. The mixture was concentrated in vacuo, the residue diluted with aqueous HCl (0.5 N) until pH=5 and evaporated again. The solid residue was triturated with dichloromethane/MeOH (10:1), filtered and the filtrate was concentrated in vacuo to yield a mixture of isomers of the title compound as a white solid. MS (ESI): m/z=419.3 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthe residue diluted with aqueous HCl (0.5 N) until pH=5
  3. customevaporated again
  4. customThe solid residue was triturated with dichloromethane/MeOH (10:1)
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated in vacuo
  7. customto yield

Sources & evidence

ORD record
ord-0a5b696bf6684e5b9a74149aee9c1c36
Source dataset
uspto-grants-2014_08
Patent number
US08815881B2

Reaction notes

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