Cyclopentanol → HCID 59578076, compound

HRID 2194204Notes

Reaction equation

HRID 2194204 reaction equation
[H-].[Na+].[CH:3]1([OH:8])[CH2:7][CH2:6][CH2:5][CH2:4]1.Cl[CH2:10][C:11]([N:13]1[CH2:34][CH2:33][C:16]2([C:20](=[O:21])[N:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)[CH2:18][CH2:17]2)[CH2:15][CH2:14]1)=[O:12]>C1COCC1.C(Cl)(Cl)Cl>[CH:3]1([O:8][CH2:10][C:11]([N:13]2[CH2:14][CH2:15][C:16]3([C:20](=[O:21])[N:19]([C:22]4[CH:27]=[CH:26][C:25]([O:28][C:29]([F:30])([F:31])[F:32])=[CH:24][CH:23]=4)[CH2:18][CH2:17]3)[CH2:33][CH2:34]2)=[O:12])[CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 7298CyclopentanolHCID 24758Sodium hydrideHCID 59577957HCID 59577957, compound

Product 1

HCID 59578076HCID 59578076, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (5 mg, 0.13 mmol) in THF (2 mL) at 0° C. was added cyclopentanol (10 uL, 0.11 mmol) and the mixture was stirred for 30 min at 0° C. A solution of 8-(2-chloro-acetyl)-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one (example 225, 42 mg, 0.11 mmol) in THF (500 uL) was added drop-wise and the reaction mixture was allowed to warm to room temperature and stirred for 16 h. The reaction mixture was diluted with chloroform and the resultant precipitate was filtered off and the filtrate was concentrated in vacuo to give the crude residue which was purified by flash column chromatography (7:3 AcOEt/heptane) which afforded the desired product as a white solid (16 mg, 34%). MS (ESI): 441.3 (MH+).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 16 h
  3. filtrationthe resultant precipitate was filtered off
  4. concentrationthe filtrate was concentrated in vacuo
  5. customto give the crude residue which
  6. customwas purified by flash column chromatography (7:3 AcOEt/heptane) which

Sources & evidence

ORD record
ord-fb741b84e3094e9ea4b81a7348519e53
Source dataset
uspto-grants-2012_12
Patent number
US08329904B2

Reaction notes

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