Dimethylformamide → HCID 19874450, compound

HRID 728908Notes

Reaction equation

HRID 728908 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[CH:11]=[C:12]([C:18]#[N:19])[C:13](=[O:17])[NH:14][C:15]=1[CH3:16].BrC[CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25].[CH3:29]N(C=O)C>>[C:24]([CH:23]([CH3:22])[CH2:29][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[CH:11]=[C:12]([C:18]#[N:19])[C:13](=[O:17])[NH:14][C:15]=1[CH3:16])([O:26][CH2:27][CH3:28])=[O:25]

Participants

5

Reactant 4

HCID 6228Dimethylformamide3×HCID 24758Sodium hydrideHCID 76300Ethyl 4-bromobutyrateHCID 19874464HCID 19874464, compound

Product 1

HCID 19874450HCID 19874450, compound

Procedure

A dispersion of 780 mg (17.7 mmol) of 60% sodium hydride in mineral oil and10 ml of DMF is treated, dropwise, with a solution of 2.00 g (8.8 mmol) of 5-(2-hydroxyphenyl)-6-methyl-2-oxo-1,2-dihydro-3-pyridine carbonitrile in 20 ml of DMF. The reaction is stirred 30 min at RT, then cooled in an ice bath and 1.72 g (8.8 mmol) of ethyl 4-bromobutyrate in 10 ml of DMF is added dropwise. The reaction is allowed to slowly come to RT and stirred overnight under N2. The mixture is then concentrated under vacuum, the residue taken up in 80 ml of water, and extracted with EtOAc (2×25 ml). The aqueous phase is acidified to pH=5 with 10% HCl and extracted with EtOAc (4×80 ml). The EtOAc extracts are dried (MgSO4) and the solvent removed to leave an orange oil. This oil is crystallized from EtOAc-hexane to give 1.61 g of 5-(2-carboethoxypropyloxyphenyl)-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile as a light yellow solid, m.p. 167°-170° C. Yield, 54%. 1H-NMR (d6 -DMSO): δ 1.18 (t,3H); 1.88 (m,2H); 2.10 (s, 3H); 2.37 (t, 2H); 3.97 (q,2H); 7.00 (t,2H); 7.10 (d,1H); 7.20 (d,1H);7.40 (t,1H); 7.97 (s,1H).

Workup

  1. temperaturecooled in an ice bath
  2. customto slowly come to RT
  3. stirringstirred overnight under N2
  4. concentrationThe mixture is then concentrated under vacuum
  5. extractionextracted with EtOAc (2×25 ml)
  6. extractionextracted with EtOAc (4×80 ml)
  7. dry with materialThe EtOAc extracts are dried (MgSO4)
  8. customthe solvent removed
  9. customto leave an orange oil
  10. customThis oil is crystallized from EtOAc-hexane

Sources & evidence

ORD record
ord-2a8fa839a28a470e860b64dadc5d638f
Source dataset
uspto-grants-1991_09
Patent number
US05051431

Reaction notes

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