Tetrahydrofuran → HCID 58417336, compound

HRID 1049076Notes

Reaction equation

HRID 1049076 reaction equation
[C:1]([S@:5](/[N:7]=[CH:8]/[C:9]1[CH:21]=[CH:20][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:11][CH:10]=1)=[O:6])([CH3:4])([CH3:3])[CH3:2].[CH2:22]1[CH2:26]OC[CH2:23]1.C([Li])(C)C.[NH4+].[Cl-]>O.CCOC(C)=O>[C:1]([S@:5]([NH:7][C@@H:8]([C:9]1[CH:10]=[CH:11][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:20][CH:21]=1)[CH:22]([CH3:26])[CH3:23])=[O:6])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 58417230HCID 58417230, compoundHCID 178506895HCID 178506895, compound

Product 1

HCID 58417336HCID 58417336, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To an oven-dried 50-mL round-bottom flask was added tert-butyl 4-[(E)-{[(R)-tert-butylsulfinyl]imino}methyl]benzoate (3.00 g, 9.70 mmol) and THF (48 mL). The solution was cooled to −78° C. then isopropyllithium (55.4 mL, 38.8 mmol, 0.70 M of in pentane) was slowly added via a syringe pump over 15 min. The resulting reaction mixture was stirred at −78° C. After 1 h, EtOAc (100 mL), sat. NH4Cl solution (20 mL), and water (10 mL) were added to the flask at this temperature. After separation, the aqueous layer was extracted with EtOAc (2×60 mL). Combined organic layers were washed with brine (20 mL), dried (MgSO4), and concentrated. Purification via flash chromatography (20% EtOAc-hexanes to 50% EtOAc-hexanes) afforded major diastereomer tert-butyl 4-[(1R)-1-{[(R)-tert-butylsulfinyl]amino}-2-methylpropyl]benzoate (1.59 g, 46%) as a white solid. [c]D20=−18.9 (c=1.0, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 7.96 (d, J=8.5 Hz, 2H), 7.31 (d, J=8.1 Hz, 2H), 4.18 (d, J=6.0 Hz, 1H), 3.45 (d, J=6.0 Hz, 1H), 2.22 (m, 1H), 1.58 (s, 9 μl), 1.24 (s, 9H), 0.94 (d, J=6.8 Hz, 3H), 0.80 (d, J=6.8 Hz, 3H).

Workup

  1. customThe resulting reaction mixture
  2. customAfter separation
  3. extractionthe aqueous layer was extracted with EtOAc (2×60 mL)
  4. washCombined organic layers were washed with brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customPurification via flash chromatography (20% EtOAc-hexanes to 50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-15c9c9e68f4f48b69141d2b970390d6e
Source dataset
uspto-grants-2016_07
Patent number
US09382197B2

Reaction notes

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