Hexamethylphosphoramide → HCID 19041732, compound

HRID 1683984Notes

Reaction equation

HRID 1683984 reaction equation
[Li]CCCC.CC1(C)CCCC(C)(C)N1.[Br:16][C:17]1[CH:44]=[CH:43][C:20]([CH2:21][N:22]2[C:30]3[C:25](=[CH:26][C:27]([O:31][CH3:32])=[CH:28][CH:29]=3)[C:24]([CH2:33][CH2:34][CH:35]([CH3:41])[C:36]([O:38][CH2:39][CH3:40])=[O:37])=[C:23]2[CH3:42])=[CH:19][CH:18]=1.CN(P(N(C)C)(N(C)C)=[O:49])C>C1COCC1>[Br:16][C:17]1[CH:44]=[CH:43][C:20]([CH2:21][N:22]2[C:30]3[C:25](=[CH:26][C:27]([O:31][CH3:32])=[CH:28][CH:29]=3)[C:24]([CH2:33][CH2:34][C:35]([OH:49])([CH3:41])[C:36]([O:38][CH2:39][CH3:40])=[O:37])=[C:23]2[CH3:42])=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 12679HexamethylphosphoramideHCID 130352,2,6,6-TetramethylpiperidineHCID 19041724HCID 19041724, compoundHCID 178418339Butyllithium

Product 1

HCID 19041732HCID 19041732, compoundYield 25.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-BuLi (1.6M in hexane, 1.5 mL, 2.4 mmol) was slowly added to 2,2,6,6-tetramethylpiperidine at 0° C. and the slurry was stirred 10 min, then cooled to -78° C. and diluted with 6 mL (oxygenated) THF. The ester from Example 3, Step 2 (880 mg, 1.92 mmol) dissolved in 3 mL THF (O2) was added and the resulting mixture was stirred-- h at -78° C. and 1 h at -45° C. HMPA (668 μL, 3.8 mmol) was added and the mixture was stirred another 2 h at -30° C., then warmed to 0° C. The reaction was quenched with aq. NaHSO3 and then partitioned between saturated NH4Cl and ethyl acetate; the organic layer was washed with water, brine and dried over MgSO4. Purification by flash chromatography (40% ethyl acetate in hexane) provided 230 mg of the title compound.

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred-- h at -78° C. and 1 h at -45° C
  3. stirringthe mixture was stirred another 2 h at -30° C.
  4. temperaturewarmed to 0° C
  5. customThe reaction was quenched with aq. NaHSO3
  6. custompartitioned between saturated NH4Cl and ethyl acetate
  7. washthe organic layer was washed with water, brine
  8. dry with materialdried over MgSO4
  9. customPurification by flash chromatography (40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-48a9b604f9684b21999b902a794fcedb
Source dataset
uspto-grants-1997_06
Patent number
US05639780

Reaction notes

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