Dimethylformamide → HCID 86713533, compound

HRID 1847131Notes

Reaction equation

HRID 1847131 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[C:5]([N:13]2[CH2:18][C@H:17]([CH3:19])[O:16][C@H:15]([CH3:20])[CH2:14]2)=[C:4]([F:21])[C:3]=1[F:22].CN(C)CCN(C)C.CN(C)[CH:33]=[O:34]>O1CCCC1.C(OC(=O)C)C>[CH3:19][C@@H:17]1[CH2:18][N:13]([C:5]2[C:6]([CH:8]3[O:12][CH2:11][CH2:10][O:9]3)=[CH:7][C:2]([CH:33]=[O:34])=[C:3]([F:22])[C:4]=2[F:21])[CH2:14][C@H:15]([CH3:20])[O:16]1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 58847137HCID 58847137, compound

Product 1

HCID 86713533HCID 86713533, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of (2R,6S)-4-(4-bromo-6-(1,3-dioxolan-2-yl)-2,3-difluorophenyl)-2,6-dimethylmorpholine (previously described in WO2004031195, page 81, 0.500 g, 1.32 mmol) and tetramethylethylene-diamine (0.12 mL, 2.12 mmol) in tetrahydrofuran (12 mL) at −78° C. is added t-buthyllithium (1.94 mL, 3.31 mmol). The reaction is stirred at −78° C. for 1.5 h and dimethylformamide is added. The reaction is stirred at −78° C. for an additional 30 min and warmed to rt. Mixture is diluted with ethylacetate (50 mL) and washed with saturated aqueous NH4Cl. (50 ml) and brine (30 mL). Dried over Na2SO4 and concentrated to give the title compound (433 mg): LCMS (M+H) 327.1.

Workup

  1. customat −78° C.
  2. additionis added t-buthyllithium (1.94 mL, 3.31 mmol)
  3. stirringThe reaction is stirred at −78° C. for an additional 30 min
  4. temperaturewarmed to rt
  5. washwashed with saturated aqueous NH4Cl
  6. dry with materialDried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-88687d6dd9ed474ea5729e7528555c94
Source dataset
uspto-grants-2015_02
Patent number
US08952149B2

Reaction notes

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