tert-Butyl acetate → HCID 91226750, compound

HRID 1818630Notes

Reaction equation

HRID 1818630 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:11]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])(=[O:13])[CH3:12].[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[N:25]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=1)[C:24]([C:39](OCC)=[O:40])=[CH:23]2.C([O-])(O)=O.[Na+]>C1COCC1>[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[N:25]([C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:36])([F:38])[F:37])[CH:30]=1)[C:24]([C:39](=[O:40])[CH2:12][C:11]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:23]2

Participants

6

Reactant 4

HCID 10908tert-Butyl acetateHCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 67482392HCID 67482392, compound

Product 1

HCID 91226750HCID 91226750, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (−78° C.) solution of LHMDS (13 mL, 1.0 M in THF, 13.0 mmol) in THF (13 mL) was added tert-butyl acetate (1.76 mL, 13.0 mmol), dropwise. After 30 min, a solution of the title compound of Example 9 Step A (1.60 g, 4.36 mmol) in THF (4 mL) was added, and the mixture was held at −78° C. for 30 min, then was placed in a 0° C. bath. After 1.5 h, the reaction mixture was poured into sat. aq. NaHCO3 and extracted twice with ethyl acetate. The combined organic phases were concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 30%, then 30 to 100% hexanes in ethyl acetate) afforded the title compound: LCMS C, tr=2.99 min, m/z 382.1 [M−tBu+H]+; 1H NMR (500 MHz, CDCl3) δ 7.74 (d, J=2.0 Hz, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.64 (t, J=8.0 Hz, 1H), 7.56 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.38 (s, 1H), 7.29 (dd, J=9.0, 2.0 Hz, 1H), 7.01 (d, J=9.0 Hz, 1H), 3.83 (s, 2H), 1.44 (s, 9H).

Workup

  1. waitthe mixture was held at −78° C. for 30 min
  2. customwas placed in a 0° C.
  3. waitAfter 1.5 h
  4. extractionextracted twice with ethyl acetate
  5. concentrationThe combined organic phases were concentrated in vacuo
  6. customPurification by flash chromatography on silica gel (0 to 30%

Sources & evidence

ORD record
ord-acc1b12e74074aca9ea52a2d205621fc
Source dataset
uspto-grants-2009_10
Patent number
US07598398B2

Reaction notes

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