Dimethylformamide dimethyl acetal → HCID 49787389, compound

HRID 415373Notes

Reaction equation

HRID 415373 reaction equation
[NH2:1][C:2]1[C:19]([C:20]#[N:21])=[CH:18][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]([NH:16][CH3:17])=[O:15])[CH2:9][CH2:8]2)=[C:4]([O:22][CH3:23])[CH:3]=1.CO[CH:26](OC)[N:27]([CH3:29])[CH3:28]>CC1CCCO1.C(O)(=O)C>[C:20]([C:19]1[C:2]([N:1]=[CH:26][N:27]([CH3:29])[CH3:28])=[CH:3][C:4]([O:22][CH3:23])=[C:5]([CH:18]=1)[O:6][CH:7]1[CH2:8][CH2:9][N:10]([CH2:13][C:14]([NH:16][CH3:17])=[O:15])[CH2:11][CH2:12]1)#[N:21]

Participants

5

Reactant 2

HCID 78373Dimethylformamide dimethyl acetal2×HCID 49787390HCID 49787390, compound

Product 1

HCID 49787389HCID 49787389, compoundYield 100.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
76 °C

Procedure

2-[4-(4-Amino-5-cyano-2-methoxyphenoxy)piperidin-1-yl]-N-methylacetamide (6, 18.21 g, 52.05 mmoles) was suspended in 2-methyltetrahydrofuran (99.62 g). To this was added acetic acid (162.79 mg), and N,N-dimethylformamide dimethyl acetal (DMF-DMA) (8.63 g, 70.27 mmoles) and the resulting reaction mixture was heated at 76° C. for 16 hrs. Additional N,N-dimethylformamide dimethyl acetal (639.41 mg, 5.20 mmoles) was added to the reaction mixture to ensure the reaction completed. The reaction mixture was cooled to 30° C. during which time crystallisation occurred. The resulting solid was isolated by filtration, washed with 2-methyltetrahydrofuran (14.23 g) and dried to afford the title compound (19.53 g, 97% yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.65 (m, 2H) 1.86 (m, 2H) 2.24 (m, 2H) 2.60 (d, J=4.7 Hz, 3H) 2.66 (m, 2H) 2.87 (s, 2H) 2.95 (s, 3H) 3.04 (s, 3H) 3.81 (s, 3H) 4.19 (tt, J=8.2, 3.8 Hz, 1H) 6.72 (s, 1H) 7.15 (s, 1H) 7.67 (q, J=4.7 Hz, 1H) 7.90 (s, 1H); Mass Spectrum: m/z (M+H)+ 374.2.

Workup

  1. customthe resulting reaction mixture
  2. temperatureThe reaction mixture was cooled to 30° C. during which time crystallisation
  3. customThe resulting solid was isolated by filtration
  4. washwashed with 2-methyltetrahydrofuran (14.23 g)
  5. customdried

Sources & evidence

ORD record
ord-24992d9cad744817867b726decf88a33
Source dataset
uspto-grants-2012_01
Patent number
US08088782B2

Reaction notes

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