Citric Acid → (S)-2-[3-tert-Butylsulfanyl-2-(2-carboxy-2-methyl-propyl)-1-(4-chloro-benzyl)-1H-indol-5-yloxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1948889Notes

Reaction equation

HRID 1948889 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH:13]([O:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27]([CH2:32][C:33]([C:36]([O:38]CC)=[O:37])([CH3:35])[CH3:34])=[C:26]2[S:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[OH-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH:13]([O:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27]([CH2:32][C:33]([C:36]([OH:38])=[O:37])([CH3:34])[CH3:35])=[C:26]2[S:41][C:42]([CH3:45])([CH3:44])[CH3:43])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 66937570(S)-2-[3-tert-Butylsulfanyl-1-(4-chloro-benzyl)-2-(2-ethoxycarbonyl-2-methyl-propyl)-1H-indol-5-yloxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 66612059(S)-2-[3-tert-Butylsulfanyl-2-(2-carboxy-2-methyl-propyl)-1-(4-chloro-benzyl)-1H-indol-5-yloxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

The ester from Step 4 (0.16 g, 0.26 mmol) was dissolved in MeOH (1 mL), THF (1 mL), and water (1 mL). Lithium hydroxide (0.6 g, 1.43 mmol) was added, and the reaction was heated for 12 hours until no starting material was seen by TLC analysis. The reaction was diluted with water, acidified to pH 5 with citric acid, and extracted with EtOAc. The combined organic layers were washed with water, dried over MgSO4, filtered, and concentrated. The residue was purified on silica gel (0 to 40% EtOAc in hexanes) to give the desired product (C-5; X=Cl).

Workup

  1. temperaturethe reaction was heated for 12 hours until no starting material
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with water
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (0 to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a1bdb619a29e4457b15e5f178bd22c42
Source dataset
uspto-grants-2013_03
Patent number
US08399666B2

Reaction notes

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