Trimethyl phosphonoacetate → 4-methoxy-2-methyl-1H-pyrrolo[2,3-b]pyridine

HRID 1445927Notes

Reaction equation

HRID 1445927 reaction equation
[CH3:1][O:2][C:3]([CH2:5]P(OC)(OC)=O)=[O:4].[CH2:12]([N:19]1[C:23]([CH3:24])=[CH:22][CH:21]=[C:20]1[CH:25]=O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][N:32]=[C:31]2[NH:35][C:36]([CH2:38]O)=[CH:37][C:30]=12>O1CCCC1>[CH3:1][O:2][C:3](=[O:4])[CH:5]=[CH:25][C:20]1[N:19]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:23]([CH3:24])=[CH:22][CH:21]=1.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][N:32]=[C:31]2[NH:35][C:36]([CH3:38])=[CH:37][C:30]=12

Participants

6

Reactant 3

HCID 80029Trimethyl phosphonoacetateHCID 15885418(4-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)methanolHCID 591703801-benzyl-5-methyl-1H-pyrrole-2-carbaldehyde

Product 2

HCID 117884674-methoxy-2-methyl-1H-pyrrolo[2,3-b]pyridineHCID 685456893-(1-benzyl-5-methyl-1H-pyrrol-2-yl)-acrylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

3-(1-Benzyl-5-methyl-1H-pyrrol-2-yl)-acrylic acid methyl ester, 5: Sodium (14.45 g, 628 mmol) was added in portions to a dry methanol (420 mL). To the fresh formed sodium methoxide solution was added dropwise the solution of trimethyl phosphonoacetate (50 mL, 302 mmol) in tetrahydrofuran (105 mL) at room temperature. After addition the mixture was stirred for additional 60 min at room temperature. Then to the reaction mixture was added dropwise the solution of 1-benzyl-5-methyl-1H-pyrrole-2-carbaldehyde, 4 (30.8 g, 154 mmol) in tetrahydrofuran (630 mL) at room temperature. The reaction mixture was stirred for 2 h at room temperature. The mixture was concentrated and redissolved in ethyl acetate (1 L). The mixture was washed with 1 M HCl solution, then saturated NaHCO3, H2O. The organic solution were dried over MgSO4 and then filtered, concentrated to afford the crude product, 3-(1-benzyl-5-methyl-1H-pyrrol-2-yl)-acrylic acid methyl ester, 5 as a light yellow solid. Yield: 40 g

Workup

  1. additionAfter addition the mixture
  2. stirringThe reaction mixture was stirred for 2 h at room temperature
  3. concentrationThe mixture was concentrated
  4. dissolutionredissolved in ethyl acetate (1 L)
  5. washThe mixture was washed with 1 M HCl solution
  6. dry with materialThe organic solution were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-57ee828bcf4b4bd18b696f731e1c3bf1
Source dataset
uspto-grants-2010_02
Patent number
US07666898B2

Reaction notes

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