Tetrahydrofuran → HCID 21251054, compound

HRID 1532507Notes

Reaction equation

HRID 1532507 reaction equation
[F:1][CH:2]([F:32])[O:3][C:4]1[CH:5]=[C:6]([CH:14]([C:16]2[CH:17]=[N:18][C:19]([N:22]([CH3:31])[C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)=[CH:20][CH:21]=2)O)[CH:7]=[CH:8][C:9]=1[O:10][CH:11]([F:13])[F:12].CCN([CH:39]([CH3:41])[CH3:40])C(C)C.[O:42]=S(Cl)Cl.[CH3:46][N:47](P(N(C)C)(N(C)C)=O)[CH3:48].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:67]1[CH2:71][O:70][CH2:69][CH2:68]1>C1(C)C=CC=CC=1>[C:71]([CH:67]([C:39]1[CH:40]=[CH:48][N:47]=[CH:46][CH:41]=1)[CH:14]([C:6]1[CH:7]=[CH:8][C:9]([O:10][CH:11]([F:13])[F:12])=[C:4]([O:3][CH:2]([F:32])[F:1])[CH:5]=1)[C:16]1[CH:17]=[N:18][C:19]([N:22]([CH3:31])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[CH:20][CH:21]=1)([O:70][CH2:69][CH3:68])=[O:42]

Participants

8

Reactant 6

HCID 8028TetrahydrofuranHCID 12679HexamethylphosphoramideHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 21251057HCID 21251057, compound

Product 1

HCID 21251054HCID 21251054, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of alcohol from Step 2 above (121 mg, 0.27 mmol) in 3 mL of toluene was added 0.113 mL (0.65 mmol) of i-Pr2NEt followed by 0.024 mL (0.32 mmol) of SOCl2. The solution was stirred 1 h at 0° C. followed by the addition of the enolate generated as follow: to a solution of ethyl 4-pyridyl acetate (178 mg, 1.08 mmol) and HMPA (0.188 mL, 11.08 mmol) in 4 mL of THF, was slowly added 2.2 mL (1.08 mmol) of a 0.5 M solution of KHMDS in toluene and the resulting solution was stirred 10 minutes at room temperature. The resulting cloudy solution was stirred 25 minutes, quenched with a saturated aqueous NH4Cl solution and diluted with ethyl acetate/saturated NaHCO3 solution. The aqueous layer was extracted with ethyl acetate and the combined organic layer were washed with water and brine, dried over MgSO4 and concentrated under reduced pressure. The residue was used directly for the next step without any purification.

Workup

  1. stirringthe resulting solution was stirred 10 minutes at room temperature
  2. stirringThe resulting cloudy solution was stirred 25 minutes
  3. customquenched with a saturated aqueous NH4Cl solution
  4. additiondiluted with ethyl acetate/saturated NaHCO3 solution
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washthe combined organic layer were washed with water and brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was used directly for the next step without any purification

Sources & evidence

ORD record
ord-64802a3fa07844f4bebfc1f15ca1d504
Source dataset
uspto-grants-2001_03
Patent number
US06200993B1

Reaction notes

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