Ethylacetate heptane → HCID 24755603, compound

HRID 244390Notes

Reaction equation

HRID 244390 reaction equation
C[Mg]Cl.[CH2:4]([C:6]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][N:13]=2)[NH:8][C:7]=1[C:15]1[CH:20]=[CH:19][C:18](CC=O)=[CH:17][CH:16]=1)[CH3:5].C([O:27][CH2:28][CH3:29])(=O)C.[CH3:30]CCCCCC>O1CCCC1>[CH2:4]([C:6]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][N:13]=2)[NH:8][C:7]=1[C:15]1[CH:20]=[CH:19][C:18]([C:28]([OH:27])([CH3:29])[CH3:30])=[CH:17][CH:16]=1)[CH3:5]

Participants

5

Reactant 3

HCID 21899848Ethylacetate heptaneHCID 86638943HCID 86638943, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 24755603HCID 24755603, compoundYield 109%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (˜5° C.) solution of methylmagnesium chloride (3M in THF; 81.3 mL, 244 mmol, 10 equiv.) in tetrahydrofuran (116 mL), was added a solution of compound 4 (6.5 g, 24.4 mmol) in tetrahydrofuran (348 mL) drop-wise, over ninety minutes, keeping the temperature at about 0° C. by the rate of addition. A bright yellow solution was observed on addition. After one hour, TLC (ethyl acetate/n-heptane 1/1) showed no starting material present and a new spot moving at a lower Rf. The batch was quenched by the careful addition of a saturated, aqueous solution of sodium bicarbonate (about 660 mL). A thick mass ensued and ethyl acetate (250 mL) and water (250 mL) were added to the mixture. The aqueous layer was removed and re-extracted with ethyl acetate (2×250 mL). The ethyl acetate fractions were combined, washed with water (2×200 mL) and concentrated on the Buchi at a bath temperature of 40° C. and from 80 to 10 torr, to give 7.5 g (109%) of 1 as a light-beige solid: 1H NMR (DMSO-d6, FIG. 2) δ 12.0 (1H, s), 8.35 (1H, d, J=3.5 Hz), 8.2 (1H, d, J=3.5 Hz), 7.6 (4H, s), 5.1 (1H, s), 2.9 (2H, q, J=8 Hz), 1.5 (6H, s), 1.3 (3H, t, J=8 Hz).

Workup

  1. waitover ninety minutes
  2. customat about 0° C.
  3. additionby the rate of addition
  4. additionA bright yellow solution was observed on addition
  5. customThe batch was quenched by the careful addition of a saturated, aqueous solution of sodium bicarbonate (about 660 mL)
  6. additionethyl acetate (250 mL) and water (250 mL) were added to the mixture
  7. customThe aqueous layer was removed
  8. extractionre-extracted with ethyl acetate (2×250 mL)
  9. washwashed with water (2×200 mL)
  10. concentrationconcentrated on the Buchi at a bath temperature of 40° C.

Sources & evidence

ORD record
ord-9ce69d6b496d4f39b01decbda43f3b04
Source dataset
uspto-grants-2014_02
Patent number
US08658649B2

Reaction notes

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