Tetrahydrofuran → HCID 69078142, compound

HRID 228133Notes

Reaction equation

HRID 228133 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([N:12]2[C@H:16]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:15][O:14][C:13]2=O)=[O:11])=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38].C1C[O:47]CC1>>[O:47]=[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:18]1[CH2:17][C@@H:16]1[CH2:15][O:14][CH2:13][N:12]1[C:10](=[O:11])[C@@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH2:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 79177tert-Butyl bromoacetateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 69077529HCID 69077529, compound

Product 1

HCID 69078142HCID 69078142, compound

Conditions

Temperature
-78 °C

Procedure

To a solution of (4R)-3-[3-(4-chlorophenyl)propanoyl]-4-benzyl-1,3-oxazolidin-2-one (Step 2) (3.0 g, 8.72 mmol) in anhydrous THF (100 mL, Aldrich) at −78° C. was added a THF solution of NaHMDS (13.1 mL, 1M, Aldrich). The solution was stirred at −78° C. for 30 min then at −20° C. for 30 min. The solution was cooled to −78° C. again and t-butyl bromoacetate (1.93 mL, 13.1 mol) was added to the reaction mixture via a syringe. The reaction was stirred at −78° C. for 2 h. After warming to RT, the reaction mixture was poured onto 1M NaH2PO4 (50 mL). The desired compound was extracted with 100 mL of EtOAc and the organic phase was washed with 50 mL of brine, dried over Na2SO4 and concentrated in vacuo. The compound was further purified with silica gel column chromatography (20% to 50% EtOAc in hexane) to provide tert-butyl 4-[(4R)-2-oxo-4-benzyl(1,3-oxazolidin-3-yl)](3S)-3-[(4-chlorophenyl)methyl]-4-oxobutanoate as a light yellow solid (3.5 g). MS (ESI, pos. ion) m/z: 458.0 (M+1). Calc'd for C25H28ClNO5: 457.17.

Workup

  1. waitat −20° C. for 30 min
  2. temperatureThe solution was cooled to −78° C. again
  3. stirringThe reaction was stirred at −78° C. for 2 h
  4. temperatureAfter warming to RT
  5. extractionThe desired compound was extracted with 100 mL of EtOAc
  6. washthe organic phase was washed with 50 mL of brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe compound was further purified with silica gel column chromatography (20% to 50% EtOAc in hexane)

Sources & evidence

ORD record
ord-65dc7703669a45739e6917d723cc82fe
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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