Lithium Hydroxide → 4-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-phenoxymethyl]-1-(3-trifluoromethyl-benzyl)-pyrrolidine-2-carboxylic acid

HRID 889061Notes

Reaction equation

HRID 889061 reaction equation
C[O:2][C:3]([CH:5]1[CH2:9][CH:8]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[NH:26][C:25]4[C:24](=[O:27])[N:23]([CH2:28][CH2:29][CH3:30])[C:22](=[O:31])[N:21]([CH2:32][CH2:33][CH3:34])[C:20]=4[N:19]=3)=[CH:14][CH:13]=2)[CH2:7][N:6]1[CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=1)=[O:4].[Li+].[OH-]>C1COCC1.CO.O>[O:31]=[C:22]1[N:21]([CH2:32][CH2:33][CH3:34])[C:20]2[N:19]=[C:18]([C:15]3[CH:14]=[CH:13][C:12]([O:11][CH2:10][CH:8]4[CH2:7][N:6]([CH2:35][C:36]5[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:44])([F:45])[F:43])[CH:37]=5)[CH:5]([C:3]([OH:4])=[O:2])[CH2:9]4)=[CH:17][CH:16]=3)[NH:26][C:25]=2[C:24](=[O:27])[N:23]1[CH2:28][CH2:29][CH3:30]

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 579887864-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-phenoxymethyl]-1-(3-trifluoromethyl-benzyl)-pyrrolidine-2-carboxylic acid methyl ester

Product 1

HCID 442364494-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-phenoxymethyl]-1-(3-trifluoromethyl-benzyl)-pyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of solution of 4-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-phenoxymethyl]-1-(3-trifluoromethyl-benzyl)-pyrrolidine-2-carboxylic acid methyl ester (25 mg, 0.039 mmol) in THF (3 ml) and MeOH (1 ml) was added aq. solution of LiOH (3 mg, 0.079 mmol) in H2O (1 ml) at 0° C. and it was stirred for 2 hrs. Reaction mixture was concentrated, residue was diluted with water and acidified with aq. HCl. The aqueous layer was extracted with ethyl acetate and washed with brine. The ethyl acetate layer was concentrated and purified by column chromatography to offer 4-[4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-phenoxymethyl]-1-(3-trifluoromethyl-benzyl)-pyrrolidine-2-carboxylic acid as viscous oil (18 mg, 75%).

Workup

  1. customReaction mixture
  2. concentrationwas concentrated
  3. additionresidue was diluted with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washwashed with brine
  6. concentrationThe ethyl acetate layer was concentrated
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-5b874389b46e498ca0ef6ccf2351a4f3
Source dataset
uspto-grants-2012_08
Patent number
US08252797B2

Reaction notes

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