Sodium hydride → HCID 59598506, compound

HRID 2266285Notes

Reaction equation

HRID 2266285 reaction equation
[H-].[Na+].[F:3][C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[CH:11]=2)=[C:8]([C@H:17]([OH:31])[C@@H:18]2[O:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]2)[CH:7]=[CH:6][CH:5]=1.BrC[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>C1COCC1>[CH2:38]([O:37][C:35](=[O:36])[CH2:34][O:31][C@@H:17]([C:8]1[CH:7]=[CH:6][CH:5]=[C:4]([F:3])[C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[CH:11]=1)[C@@H:18]1[O:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:19]1)[CH3:39]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 68320Ethyl 3-bromopropionateHCID 59598471HCID 59598471, compound

Product 1

HCID 59598506HCID 59598506, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a slurry of 60% NaH in oil (0.75 g, 18.7 mmol) in THF (30 mL) was added a solution of (R)-tert-butyl 2-((S)-(6-fluoro-3′-methylbiphenyl-2-yl)(hydroxy)methyl)morpholine-4-carboxylate (2.5 g, 6.23 mmol) in THF (20 mL) dropwise at and then the reaction mixture was stirred for about 1 h at rt. A solution of ethyl 3-bromopropionate (1.55 g, 9.35 mmol) in THF (20 mL) was added dropwise while the temperature was maintained at −15 to −5° C. The mixture was allowed to warm slowly to rt and stirred for ˜2 h until the reaction was complete by tlc analysis. The reaction was cooled in an ice bath, quenched with satd aq NH4Cl (120 mL) and extracted with EtOAc. The combined organic extracts were washed with brine, dried over NaSO4, concentrated and purified by flash chromatography to afford (R)-tert-butyl 2-((S)-(2-ethoxy-2-oxoethoxy)(6-fluoro-3′-methylbiphenyl-2-yl)methyl)morpholine-4-carboxylate (570 mg, 19%). MS (E/Z): 488 (M+H+)

Workup

  1. temperaturewas maintained at −15 to −5° C
  2. temperatureto warm slowly to rt
  3. stirringstirred for ˜2 h until the reaction
  4. temperatureThe reaction was cooled in an ice bath
  5. customquenched with satd aq NH4Cl (120 mL)
  6. extractionextracted with EtOAc
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over NaSO4
  9. concentrationconcentrated
  10. custompurified by flash chromatography

Sources & evidence

ORD record
ord-a22248e04e5d45989a6e95bbac8a941c
Source dataset
uspto-grants-2010_12
Patent number
US07858624B2

Reaction notes

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