Dimethylamine → N,N-dimethyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)acetamide

HRID 243566Notes

Reaction equation

HRID 243566 reaction equation
C[CH2:2][N:3](CC)[CH2:4]C.[CH3:8][N:9](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)[CH3:10].[B-](F)(F)(F)F.[O:30]1[C:34]2([CH2:39][CH2:38][CH:37]([CH2:40][C:41]([OH:43])=O)[CH2:36][CH2:35]2)[O:33][CH2:32][CH2:31]1.CNC>CN(C=O)C.C1COCC1>[CH3:2][N:3]([CH3:4])[C:41](=[O:43])[CH2:40][CH:37]1[CH2:38][CH2:39][C:34]2([O:33][CH2:32][CH2:31][O:30]2)[CH2:35][CH2:36]1.[CH3:8][N:9]([CH3:10])[C:41](=[O:43])[CH2:40][CH:37]1[CH2:38][CH2:39][C:34](=[O:33])[CH2:35][CH2:36]1

Participants

8

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 151011212-(1,4-Dioxaspiro(4.5)decan-8-yl)acetic acid

Product 2

HCID 59442805N,N-dimethyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)acetamideHCID 59442836N,N-dimethyl-2-(4-oxocyclohexyl)acetamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

NEt3 (2.0 ml) and TBTU (2.56 g) are added to a solution of 2-(1,4-dioxaspiro[4.5]decan-8-yl)acetic acid (1.45 g; see J. Med. Chem. 1998, 41(5), 760) in DMF (50 ml) and the mixture is stirred for 30 min. 2 M Dimethylamine in THF (7.24 ml) is added. The reaction mixture is stirred for one hour and the solvent is removed under reduced pressure. The residue is dissolved in EtOAc and washed with water and aqueous citric acid (10%, 2×). The organic layer is dried (Na2SO4) and filtered, and the solvent is removed under reduced pressure. The crude product is purified using reverse phase HPLC (Varian C18 Microsorb) eluting with a gradient of 10-100% acetonitrile in water containing 0.2% trifluoroacetic acid to give N,N-dimethyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)acetamide (400 mg) and N,N-dimethyl-2-(4-oxocyclohexyl)acetamide (420 mg).

Workup

  1. stirringThe reaction mixture is stirred for one hour
  2. customthe solvent is removed under reduced pressure
  3. dissolutionThe residue is dissolved in EtOAc
  4. washwashed with water and aqueous citric acid (10%, 2×)
  5. dry with materialThe organic layer is dried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent is removed under reduced pressure
  8. customThe crude product is purified
  9. washeluting with a gradient of 10-100% acetonitrile in water containing 0.2% trifluoroacetic acid

Sources & evidence

ORD record
ord-5f3c4ec7742b428bbae9689e0624cbbe
Source dataset
uspto-grants-2014_02
Patent number
US08653262B2

Reaction notes

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