2-Chloromethyl 2-(trimethylsilyl)ethyl ether → HCID 58000310, compound

HRID 2217968Notes

Reaction equation

HRID 2217968 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:36][Si:37]([CH3:44])([CH3:43])[CH2:38][CH2:39][O:40][CH2:41]Cl>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([C:11]2([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])[CH2:16][CH2:15][C:14](=[O:17])[CH:13]([CH2:41][O:40][CH2:39][CH2:38][Si:37]([CH3:44])([CH3:43])[CH3:36])[CH2:12]2)(=[O:9])=[O:10])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 2733832Lithium HexamethyldisilazideHCID 104301374-(4-chlorophenyl)sulfonyl-4-(2,5-difluorophenyl)cyclohexan-1-one

Product 1

HCID 58000310HCID 58000310, compoundYield 44.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

4-[(4-Chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexanone (WO 02/081435) (2.0 g, 5.2 mmol) in dry tetrahydrofuran (10 mL) was added dropwise to a cooled solution of 0.5 M lithium hexamethyldisilazide in tetrahydrofuran (11.4 mL) at −78° C. The mixture was stirred at this temperature for 2 hours before adding 2-(trimethylsilyl)ethoxymethyl chloride (1.4 mL, 7.8 mmol) and the solution allowed to warm to rt. over 16 hours. The reaction mixture was diluted with ethyl acetate (10 mL), washed with water (10 mL), and the organic phase separated, dried (MgSO4) and evaporated to dryness. The product was purified on silica eluting with [9:1] hexane-ethyl acetate to yield 1.2 g of the title compound. 1H NMR CDCl3 7.38 (4H, s), 7.24-7.16 (1H, m), 7.12-7.06 (1H, m), 6.97-6.87 (1H, m), 3.66 (1H, dd, J=9.7 and 3.0 Hz), 3.51-3.45 (3H, m), 3.17-3.15 (1H, m), 3.05-2.98 (1H, m), 2.56-2.49 (2H, m),241-2.35 (2H, m), 2.23-2.17 (1H, m), 0.91-0.87 (2H, m) and 0.03 (9H, s).

Workup

  1. waitover 16 hours
  2. washwashed with water (10 mL)
  3. customthe organic phase separated
  4. dry with materialdried (MgSO4)
  5. customevaporated to dryness
  6. customThe product was purified on silica eluting with [9:1] hexane-ethyl acetate

Sources & evidence

ORD record
ord-5348d71d92b84682a9e34e5f8fb4ccb8
Source dataset
uspto-grants-2008_08
Patent number
US07410964B2

Reaction notes

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