Water → 5-chloro-N-[1,3-dioxo-2-(4-piperidinyl)-2,3-dihydro-1H-isoindol-4-yl]-2-thiophenecarboxamide

HRID 1455681Notes

Reaction equation

HRID 1455681 reaction equation
C(O)(C(F)(F)F)=O.O.[Cl:9][C:10]1[S:14][C:13]([C:15]([NH:17][C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[C:20](=[O:41])[N:21]([CH:28]2[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]2)[C:22]3=[O:27])=[O:16])=[CH:12][CH:11]=1>C(Cl)(Cl)Cl>[Cl:9][C:10]1[S:14][C:13]([C:15]([NH:17][C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[C:20](=[O:41])[N:21]([CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[C:22]3=[O:27])=[O:16])=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 18440735tert-Butyl 4-(4-{[(5-chloro-2-thienyl)carbonyl]amino}-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)tetrahydro-1(2H)-pyridinecarboxylate

Product 1

HCID 120748935-chloro-N-[1,3-dioxo-2-(4-piperidinyl)-2,3-dihydro-1H-isoindol-4-yl]-2-thiophenecarboxamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

50 ml of a mixture of TFA and water (9:1) are added dropwise to an ice-cooled mixture of 1.82 g (3.71 mmol) of tert-butyl 4-(4-{[(5-chloro-2-thienyl)carbonyl]-amino}-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)tetrahydro-1(2H)-pyridine-carboxylate in 50 ml of chloroform. The ice-cooling is removed and the mixture is stirred at room temperature for 1.5 h and then concentrated. The residue is taken up in dichloromethane/methanol and washed with sat. sodium bicarbonate solution, dried over magnesium sulfate and concentrated. The crude product can be purified further by crystallization with ether. Yield: 1.185 g (78% of theory); MS (DCI, NH4): m/z (%)=390 (M+H, 100).

Workup

  1. temperaturecooled
  2. customis removed
  3. concentrationconcentrated
  4. washwashed with sat. sodium bicarbonate solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe crude product can be purified further by crystallization with ether

Sources & evidence

ORD record
ord-d188d57c8ea34dc2adff32540031c438
Source dataset
uspto-grants-2009_01
Patent number
US07482472B2

Reaction notes

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