Methanol → HCID 59118190, compound

HRID 432097Notes

Reaction equation

HRID 432097 reaction equation
C(OC([N:8]([CH2:26][C@H:27]1[CH2:36][CH2:35][C:34]2[C:29](=[CH:30][CH:31]=[C:32]([CH2:37][C:38]3[CH:47]=[CH:46][C:41]([C:42]([O:44]C)=[O:43])=[CH:40][CH:39]=3)[CH:33]=2)[O:28]1)[CH2:9][C@@H:10]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)[O:11][SiH2]C(C)(C)C(C)(C)C)=O)(C)(C)C.[Li+].[OH-].CO.P(=O)(O)(O)O>O1CCCC1>[OH:11][C@H:10]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)[CH2:9][NH:8][CH2:26][C@H:27]1[CH2:36][CH2:35][C:34]2[C:29](=[CH:30][CH:31]=[C:32]([CH2:37][C:38]3[CH:47]=[CH:46][C:41]([C:42]([OH:44])=[O:43])=[CH:40][CH:39]=3)[CH:33]=2)[O:28]1

Participants

6

Reactant 4

HCID 887MethanolHCID 1004Phosphoric AcidHCID 3939Lithium HydroxideHCID 178497661HCID 178497661, compound

Product 1

HCID 59118190HCID 59118190, compoundYield 35.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 77.2 mg (0.11 mmol) methyl 4-[((2R)-2-{[(tert-butoxycarbonyl)((2R)-2-(3-pyridinyl)-2-{[(1,1,2,2-tetramethylpropyl)silyl]oxy}ethyl)amino]-methyl}-3,4-dihydro-2H-chromen-6-yl)methyl]benzoate (Example 167) in 1 mL of tetrahydrofuran was added 0.54 mL of 1M LiOH and 0.27 mL methanol. The mixture was stirred at room temperature for 3 hours after which point 0.5 mL of 1N phosphoric acid was added to the solution. The mixture was partitioned between ethyl acetate (3×5 mL) and water (5 mL). The organic layer was washed with saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated. To the residue was added 0.4 mL of hydrochloric acid in dioxane. This solution was stirred at room temperature for 0.5 hour. The solution was then washed with water and concentrated in vacuo, followed by purification by preparative HPLC (gradient of 100:0 0.1% TFA/H2O:acetonitrile to 30:70 0.1% TFA/H2O:acetonitrile) to obtain 16.4 mg of product as the TFA salt. MH+419.3. 1H NMR (DMSO d6, δ): 8.89 (br. s, 1H), 8.63 (s, 1H), 8.57 (d, 1H), 7.88 (dt, 1H), 7.85 (s, 1H), 7.82 (s, 1H), 7.50 (dd, 1H), 7.32 (s, 1H), 7.29 (s, 1H), 6.96 (m, 2H), 6.73 (d, 1H), 6.38 (br. s, 1H), 5.08 (m, 1H), 4.38 (m, 1H), 2.76 (m, 1H), 2.71 (m, 1H), 1.99 (m, 1H), 1.67 (m, 1H).

Workup

  1. additionwas added to the solution
  2. customThe mixture was partitioned between ethyl acetate (3×5 mL) and water (5 mL)
  3. washThe organic layer was washed with saturated sodium chloride
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionTo the residue was added 0.4 mL of hydrochloric acid in dioxane
  8. stirringThis solution was stirred at room temperature for 0.5 hour
  9. washThe solution was then washed with water
  10. concentrationconcentrated in vacuo
  11. customfollowed by purification by preparative HPLC (gradient of 100:0 0.1% TFA/H2O:acetonitrile to 30:70 0.1% TFA/H2O:acetonitrile)

Sources & evidence

ORD record
ord-c012d0efdd4b4a4d809d9d56ec689b8a
Source dataset
uspto-grants-2003_12
Patent number
US06660752B2

Reaction notes

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