Diethyl Oxalate → 1-(tert-Butyl) 2-ethyl 2-hydroxy-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1,2-dicarboxylate

HRID 392087Notes

Reaction equation

HRID 392087 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[C:21](OCC)(=[O:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23]>C1COCC1>[OH:27][C:21]1([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:15][C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]

Participants

5

Reactant 3

HCID 7268Diethyl OxalateHCID 117458482-(N-Boc-Amino)-3-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 218687431-(tert-Butyl) 2-ethyl 2-hydroxy-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-1,2-dicarboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 2-tert-butoxycarbonylamino-3-methylpyridine (1.0 g, 4.8 mmol) in THF (10 mL) at −10° C. under Ar was added dropwise a solution of n-butyllithium (1.6 M, 6.0 mL, 9.6 mmol). The mixture was stirred for 30 min then added dropwise via cannula to a stirred solution of diethyl oxalate (2.1 g, 14.4 mmol) in THF (10 mL) at 0° C. under Ar. The mixture was stirred for 1 h and partitioned between water (50 mL) and ethyl acetate (30 mL). The aqueous layer was extracted with ethyl acetate (20 mL). The combined organic extracts were washed (water, brine), dried (sodium sulfate), concentrated in vacuo and purified by column chromatography [SiO2; ethyl acetate-heptane (1:1)] to give the product as a clear oil (0.61 g, 47%). IR νmax (film)/cm−1 3475, 2982, 2935, 2237, 1740, 1695, 1606, 1592, 1433, 1371, 1310, 1248, 1209, 1188, 1159, 1099, 1065, 1023, 912, 855, 785, 770, 732 and 645; NMR δH (400 MHz, CDCl3) 1.27 (3H, t, J 7Hz), 1.53 (9H, s), 3.18 (1H, d, J 17 Hz), 3.40 (1H, d, J 17 Hz), 4.27 (2H, q, J 7 Hz), 6.90 (1H, dd, J, 2.5,5 Hz), 7.43 (1H, d, J 7 Hz), 8.26 (1H, d, J 3.5 Hz).

Workup

  1. stirringThe mixture was stirred for 1 h
  2. custompartitioned between water (50 mL) and ethyl acetate (30 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  4. washThe combined organic extracts were washed (water, brine)
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography [SiO2; ethyl acetate-heptane (1:1)]

Sources & evidence

ORD record
ord-27e071c91f79461b95900bb91ecbf6b9
Source dataset
uspto-grants-2004_10
Patent number
US06800627B1

Reaction notes

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