Hydrochloric Acid → (2-fluoro-4-{2-[(1S,2R)-2-(1-{[(1-methylcyclopropyl)oxy]carbonyl}piperidin-4-yl)cyclopropyl]ethoxy}phenyl)acetic acid

HRID 1850761Notes

Reaction equation

HRID 1850761 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[CH2:27][C:28]([O:30]C)=[O:29])[O:5][CH2:6][CH2:7][C@@H:8]1[CH2:10][C@@H:9]1[CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]2([CH3:23])[CH2:22][CH2:21]2)=[O:18])[CH2:13][CH2:12]1.CO.[OH-].[Li+].Cl>O1CCCC1.O>[F:1][C:2]1[CH:3]=[C:4]([O:5][CH2:6][CH2:7][C@@H:8]2[CH2:10][C@@H:9]2[CH:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]3([CH3:23])[CH2:21][CH2:22]3)=[O:18])[CH2:15][CH2:16]2)[CH:24]=[CH:25][C:26]=1[CH2:27][C:28]([OH:30])=[O:29]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 867111961-methylcyclopropyl 4-[(1R,2S)-2-{2-[3-fluoro-4-(2-methoxy-2-oxoethyl)phenoxy]ethyl}cyclopropyl]piperidine-1-carboxylate

Product 1

HCID 86711197(2-fluoro-4-{2-[(1S,2R)-2-(1-{[(1-methylcyclopropyl)oxy]carbonyl}piperidin-4-yl)cyclopropyl]ethoxy}phenyl)acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-methylcyclopropyl 4-[(1R,2S)-2-{2-[3-fluoro-4-(2-methoxy-2-oxoethyl)phenoxy]ethyl}cyclopropyl]piperidine-1-carboxylate (0.450 g, 1.04 mmol) in 14 ml anhydrous tetrahydrofuran was added by 7 ml methanol and 7 ml water. Lithium hydroxide (0.393 g, 16.39 mmol) was added into the reaction mixture, and the reaction was stirred at RT overnight. 1 M hydrochloric acid was added to adjust the pH to 4. The volatiles were removed under vacuum, and the remaining aqueous layer was extracted with dichloromethane (3×50 ml). The organics were combined, dried over magnesium sulphate, filtered, and the filtrate concentrated under reduced pressure. The residue was purified on Biotage column (50 g silica gel) using a gradient eluent of 0-70% ethyl acetate in hexanes (700 ml) to afford the title compound. LC/MS (m/z) 420.2 (M+H)+.

Workup

  1. customThe volatiles were removed under vacuum
  2. extractionthe remaining aqueous layer was extracted with dichloromethane (3×50 ml)
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customThe residue was purified on Biotage column (50 g silica gel)

Sources & evidence

ORD record
ord-eae9e494dbdd46f78b49e0c8395b6328
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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