Hydrochloric Acid → HCID 69073332, compound

HRID 1869730Notes

Reaction equation

HRID 1869730 reaction equation
[Li+].[OH-].[CH:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][CH:15]([CH:18]([CH3:24])[C:19]([O:21]CC)=[O:20])[CH2:14][CH:13]2[C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=2)=[CH:8][CH:7]=1)([CH3:5])[CH3:4].O1CCOCC1.Cl>O.C1COCC1>[CH:3]([C:6]1[CH:7]=[CH:8][C:9]([N:12]2[CH2:17][CH2:16][CH:15]([CH:18]([CH3:24])[C:19]([OH:21])=[O:20])[CH2:14][CH:13]2[C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:27][CH:26]=2)=[CH:10][CH:11]=1)([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium Hydroxide2×HCID 312751,4-DioxaneHCID 76697412HCID 76697412, compound

Product 1

HCID 69073332HCID 69073332, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

A solution of LiOH (27 mg, 1.1 mmol) in H2O (0.5 ml) was added to a stirred solution of the ester (Step 1, 100 mg, 0.22 mmol) in THF (1 ml) at room temperature. After 60 hours an extra portion of LiOH (30 mg) and dioxane (1 ml) were added. The mixture was heated at 110° C. for 16 hours. After cooling to room temperature the mixture was acidified with 5N HCl. The mixture was partitioned between EtOAc/H2O. The layers were separated and the aqueous layer was further extracted with EtOAc (×2). The combined extracts were washed with brine (×1), dried (Na2SO4), filtered and evaporated. The residue was purified by reverse phase HPLC to give the acid as a 3:2 mixture of diastereomers (90 mg, 94%) as colourless solid. 1H NMR (500 MHz, CDCl3) δ: 1.12-1.14 (6H, m), 1.21-1.26 (3H, m), 2.01-2.25 (3H, m), 2.26-2.40 (1H, m), 2.50-2.59 (2H, m), 2.78-2.83 (1H, m), 3.48-3.51 (1H, m), 3.91-3.95 (1H, m), 4.35-4.40 (1H, m), 7.12-7.14 (2H, m), 7.24-7.26 (2H, m), 7.42-7.53 (4H, m); M/Z (ES+) 420 (MH+).

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. customThe mixture was partitioned between EtOAc/H2O
  3. customThe layers were separated
  4. extractionthe aqueous layer was further extracted with EtOAc (×2)
  5. washThe combined extracts were washed with brine (×1)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by reverse phase HPLC
  10. customto give the acid
  11. additionas a 3:2 mixture of diastereomers (90 mg, 94%) as colourless solid

Sources & evidence

ORD record
ord-a583d2123d2b49af9a9f1612c4f305fb
Source dataset
uspto-grants-2009_12
Patent number
US07638629B2

Reaction notes

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