Methanol → HCID 58280450, compound

HRID 1879476Notes

Reaction equation

HRID 1879476 reaction equation
C([O:3][C:4]([CH:6]1[CH2:10][CH2:9][S:8](=[O:12])(=[O:11])[N:7]1[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]([CH2:32][C:33]2[C:38]([Cl:39])=[CH:37][CH:36]=[C:35]([O:40][CH3:41])[C:34]=2[F:42])[C@H:22]([CH2:28][N:29]([CH3:31])[CH3:30])[CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:15]=1)=[O:5])C.O.[OH-].[Li+].CO>O1CCCC1>[Cl:39][C:38]1[C:33]([CH2:32][N:21]([CH2:20][C:16]2[CH:15]=[C:14]([CH:19]=[CH:18][CH:17]=2)[CH2:13][N:7]2[CH:6]([C:4]([OH:5])=[O:3])[CH2:10][CH2:9][S:8]2(=[O:12])=[O:11])[C@H:22]([CH2:28][N:29]([CH3:30])[CH3:31])[CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[C:34]([F:42])[C:35]([O:40][CH3:41])=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 58280466HCID 58280466, compound

Product 1

HCID 58280450HCID 58280450, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester (0.865 g, 1.4 mmol) was dissolved in tetrahydrofuran (5.6 mL). Water (5.6 mL) and lithium hydroxide (0.050 g, 2.07 mmol) and methanol (1.2 mL) were added. The reaction was stirred at room temperature for 2.5 hours after which the reaction was concentrated under reduced pressure. To the residue was added dichloromethane and aqueous hydrochloric acid (pH˜7) resulting in an emulsion. The reaction was then concentrated to dryness under reduced pressure. The crude material was purified by supercritical fluid chromatography into the corresponding Epimer 1 and Epimer 2 of 2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid (0.084 g (Epimer 1) and 0.089 g (Epimer 2), respectively, 99% (combined yield)).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. additionTo the residue was added dichloromethane and aqueous hydrochloric acid (pH˜7)
  3. customresulting in an emulsion
  4. concentrationThe reaction was then concentrated to dryness under reduced pressure
  5. customThe crude material was purified by supercritical fluid chromatography into the corresponding Epimer 1 and Epimer 2 of 2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid (0.084 g (Epimer 1) and 0.089 g (Epimer 2)
  6. customrespectively, 99% (combined yield))

Sources & evidence

ORD record
ord-e014677589b749e5bce43065a1617c9e
Source dataset
uspto-grants-2012_11
Patent number
US08314250B2

Reaction notes

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