Sodium Hydroxide → HCID 68557074, compound

HRID 1804841Notes

Reaction equation

HRID 1804841 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([CH:14]([CH3:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:21][CH3:22].[Cl:23]N1C(=O)CCC1=O.[OH-].[Na+]>CC(O)=O.O.CCOCC>[Cl:23][C:6]1[CH:7]=[C:2]([Cl:1])[C:3]([O:21][CH3:22])=[CH:4][C:5]=1[N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([CH3:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:10][CH2:9]1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 31398ChlorosuccinimideHCID 68556209HCID 68556209, compound

Product 1

HCID 68557074HCID 68557074, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

A sample of ethyl 2-(1-(4-chloro-3-methoxyphenyl)piperidin-4-yl)propanoate (130 mg, 0.359 mmol) was suspended in glacial AcOH (4 mL) and water (0.5 mL). The resultant solution was treated with N-chlorosuccinimide (62.3 mg, 0.467 mmol) and then stirred at RT overnight. After this time, the mixture was diluted with water (10 mL) and Et2O (25 mL) and the pH was adjusted to pH 9 using 6 M NaOH (aq). The phases were separated and the aqueous phase was extracted with Et2O. The extracts were combined, washed with brine, dried (MgSO4) and concentrated on a rotary evaporator. The resultant residue was purified by flash chromatography using a 12 g silica gel cartridge and gradient elution from 10:1 Hex/EtOAc to 5:1 Hex/EtOAc. The fractions containing the product were pooled and concentrated on a rotary evaporator to give ethyl 2-(1-(2,4-dichloro-5-methoxyphenyl)piperidin-4-yl)propanoate (80 mg, 0.222 mmol, 62% yield) as an oil. 1H-NMR (500 MHz, CDCl3) δ ppm 7.32 (1 H, s), 6.58 (1 H, s), 4.15 (2 H, qd, J=7.06, 1.92 Hz), 3.87 (3 H, s), 3.34-3.41 (2 H, m), 2.60 (2 H, t, J=11.55 Hz), 2.33 (1 H, dt, J=14.30, 7.15 Hz), 1.81 (1 H, dt, J=12.92, 2.61 Hz), 1.65-1.73 (2 H, m), 1.44-1.62 (2 H, m), 1.27 (3 H, t, J=7.15 Hz), 1.16 (3 H, d, J=7.15 Hz). LC-MS: 360, [M+H]; tR=4.28 min (method b).

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase was extracted with Et2O
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated on a rotary evaporator
  6. customThe resultant residue was purified by flash chromatography
  7. washa 12 g silica gel cartridge and gradient elution from 10:1 Hex/EtOAc to 5:1 Hex/EtOAc
  8. additionThe fractions containing the product
  9. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-73a19f99634d48968a9136e5077ae048
Source dataset
uspto-grants-2013_01
Patent number
US08354432B2

Reaction notes

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