Hydrochloric Acid → Tert-butyl[(1s,2s)-1-{[(3s)-3-fluoropyrrolidin-1-yl]carbonyl}-2-(4-hydroxyphenyl)propyl]carbamate

HRID 2242646Notes

Reaction equation

HRID 2242646 reaction equation
[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([C@@H:9]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C@H:10]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[CH3:11])=[O:8])[CH2:3]1.[OH:35]O.[OH-].[Na+].Cl>C1COCC1.O>[C:30]([O:29][C:28](=[O:34])[NH:27][C@H:9]([C:7]([N:4]1[CH2:5][CH2:6][C@H:2]([F:1])[CH2:3]1)=[O:8])[C@H:10]([C:12]1[CH:13]=[CH:14][C:15]([OH:35])=[CH:16][CH:17]=1)[CH3:11])([CH3:31])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 69371253Tert-butyl{(1s,2s)-1-{[(3s)-3-fluoropyrrolidin-1-yl]carbonyl}-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propyl}carbamate

Product 1

HCID 91113754Tert-butyl[(1s,2s)-1-{[(3s)-3-fluoropyrrolidin-1-yl]carbonyl}-2-(4-hydroxyphenyl)propyl]carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the material from Step A (0.5 g, 1.0 mmol) in THF (10 mL) at 0° C. was added sequentially 30% hydrogen peroxide (0.18 mL, 1.5 mmol) and 3N aqueous sodium hydroxide (0.35 g, 1.0 mmol). After 2 h at this temperature water (30 mL) was added, and the resulting solution was adjusted to pH 5 by the addition of 1N hydrochloric acid. The mixture was extracted with ethyl acetate, and the combined extracts were washed with saturated sodium thiosulfate until the organic phase showed a negative peroxide test. The combined organics were washed with brine, dried (magnesium sulfate), and concentrated in vacuo. The residue was purified by silica gel chromatography (50% ethyl acetate in hexane) to give the title compound as a white foam. LC/MS 389.3 (M+Na).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washthe combined extracts were washed with saturated sodium thiosulfate until the organic phase
  3. washThe combined organics were washed with brine
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-2dcbd37f157f433fb115ea5bd1292eb0
Source dataset
uspto-grants-2010_03
Patent number
US07671073B2

Reaction notes

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