Methanol → HCID 59636036, compound

HRID 563905Notes

Reaction equation

HRID 563905 reaction equation
[NH2:1][C@H:2]1[C@:12]2([CH3:14])[O:13][C@@:4]3([C@H:15]4[C@H:8]([N:9]([C:17]5[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[C:19]([C:25]([F:28])([F:27])[F:26])[CH:18]=5)[C:10](=[O:16])[C@@H:11]24)[O:7][CH2:6][CH2:5]3)[CH2:3]1.[C:29](N1C=CN=C1)(N1C=CN=C1)=[O:30].[CH3:41][OH:42].C[O-].[Na+]>C1COCC1>[C:21]([C:20]1[CH:23]=[CH:24][C:17]([N:9]2[C@H:8]3[C@H:15]4[C@H:11]([C@@:12]5([CH3:14])[O:13][C@:4]4([CH2:5][CH2:6][O:7]3)[CH2:3][C@H:2]5[NH:1][C:29](=[O:30])[O:42][CH3:41])[C:10]2=[O:16])=[CH:18][C:19]=1[C:25]([F:26])([F:27])[F:28])#[N:22]

Participants

6

Reactant 4

HCID 887MethanolHCID 682631,1'-CarbonyldiimidazoleHCID 10942334Sodium MethoxideHCID 59635958HCID 59635958, compound

Product 1

HCID 59636036HCID 59636036, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Example 13 (1.18 g, 3.0 mmol) in THF (10 mL) was added drop wise over 10 min to a solution of carbonyldiimidazole (1.5 g, 9.25 mmol) in THF (10 mL). The mixture was stirred for 30 min. Next, MeOH (20 mL) was added followed by the addition of NaOMe (0.162 g, 3 mmol). The reaction mixture was stirred for 5 min and then concentrated in vacuo. To the residue was added EtOAc and washed twice with 1M HCl and once with sat. NaHCO3 aq. The organic layer was dried over MgSO4, filtered, and then concentrated in vacuo. The residue was purified by silica gel chromatography on a 120 g ISCO column eluting with a gradient from 100% CH2Cl2 up to 6% MeOH/CH2Cl2. The product was collected, concentrated in vacuo, and dried to give 1.2 g of Example 14.

Workup

  1. customwise over 10 min
  2. stirringThe reaction mixture was stirred for 5 min
  3. concentrationconcentrated in vacuo
  4. additionTo the residue was added EtOAc
  5. washwashed twice with 1M HCl and once with sat. NaHCO3 aq. The organic layer
  6. dry with materialwas dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography on a 120 g ISCO column
  10. washeluting with a gradient from 100% CH2Cl2 up to 6% MeOH/CH2Cl2
  11. customThe product was collected
  12. concentrationconcentrated in vacuo
  13. customdried

Sources & evidence

ORD record
ord-89682a52b5524e74afd33c936b9b00d9
Source dataset
uspto-grants-2011_11
Patent number
US08067582B2

Reaction notes

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