Methanol → HCID 11518161, compound

HRID 2221100Notes

Reaction equation

HRID 2221100 reaction equation
[CH2:1]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:15][CH:16]=2)[CH2:11][CH:10]([NH:24][S:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(=[O:27])=[O:26])[C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO>C1COCC1>[CH2:1]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:15][CH:16]=2)[CH2:11][CH:10]([NH:24][S:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(=[O:27])=[O:26])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 11712496HCID 11712496, compound

Product 1

HCID 11518161HCID 11518161, compoundYield 91.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3I (80 mg, 0.17 mmol) in THF (1 mL) at RT under argon was added borane-tetrahydrofuran complex (0.85 mL, 0.85 mmol) dropwise. After the addition, the reaction became a clear solution. The reaction was allowed to stir at RT under argon for 1 h. After this time, no starting material was detected by LC-MS. MeOH (1 mL) was added carefully to the reaction and the reaction was stirred at RT for overnight. The solvent was concentrated. The resultant residue was partitioned between CH2Cl2 and saturated aqueous NaHCO3 (20 mL). The layers were separated. The aqueous layer was extracted with CH2Cl2 (20 mL×3). The combined organics were washed with saturated NaCl, dried over Na2SO4, filtered and concentrated. The resultant residue was purified by silica gel (10 g) column chromatography eluting with a gradient of EtOAc (0-60%) in hexane to give the title compound as a white foam (71 mg, 88%). LC/MS (method A): retention time=2.69 min, (M+H)+=456. 1H-NMR (CDCl3, 400 MHz): δ8.00 (s, 1H), 7.75-7.85 (m, 4H), 7.47-7.55 (m, 1H), 7.10-7.48 (m, 11H), 5.44 (d, J=8.2 Hz, 1H), 4.30 (dd, J1=90 Hz, J2=16.4 Hz, 2H), 3.80-3.90 (m, 1H), 3.35-3.45 (m, 1H), 3.10 (dd, J1=4.9 Hz, J2=1.8 Hz, 1H), 2.93 (dd, J1=16.7 Hz, J2=4.5Hz, 1H), 2.65 (dd, J1=4.9 Hz, J2=1.8 Hz, 1H).

Workup

  1. additionwas added borane-tetrahydrofuran complex (0.85 mL, 0.85 mmol) dropwise
  2. additionAfter the addition
  3. stirringthe reaction was stirred at RT for overnight
  4. concentrationThe solvent was concentrated
  5. customThe resultant residue was partitioned between CH2Cl2 and saturated aqueous NaHCO3 (20 mL)
  6. customThe layers were separated
  7. extractionThe aqueous layer was extracted with CH2Cl2 (20 mL×3)
  8. washThe combined organics were washed with saturated NaCl
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resultant residue was purified by silica gel (10 g) column chromatography
  13. washeluting with a gradient of EtOAc (0-60%) in hexane

Sources & evidence

ORD record
ord-61f8f66d163647dcb26f56fa10ceeea9
Source dataset
uspto-grants-2008_05
Patent number
US07368458B2

Reaction notes

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