Chlorotrimethylsilane → HCID 18395016, compound

HRID 1602980Notes

Reaction equation

HRID 1602980 reaction equation
[NH2:1][C@@H:2]([C:7]([OH:9])=[O:8])[C:3]([CH3:6])([CH3:5])[CH3:4].CN1CCOCC1.Cl[Si](C)(C)C.C(N(C(C)C)CC)(C)C.[Cl:31][C:32]1[CH:48]=[CH:47][C:35]([O:36][C:37]2[CH:42]=[CH:41][C:40]([S:43](Cl)(=[O:45])=[O:44])=[CH:39][CH:38]=2)=[CH:34][CH:33]=1>ClCCl.CN(C=O)C>[Cl:31][C:32]1[CH:48]=[CH:47][C:35]([O:36][C:37]2[CH:38]=[CH:39][C:40]([S:43]([NH:1][C@@H:2]([C:7]([OH:9])=[O:8])[C:3]([CH3:6])([CH3:5])[CH3:4])(=[O:45])=[O:44])=[CH:41][CH:42]=2)=[CH:34][CH:33]=1

Participants

8

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 79724-MethylmorpholineHCID 81531DiisopropylethylamineHCID 27577504-(4-Chlorophenoxy)benzene-1-sulfonyl chlorideHCID 6950340D-tert-leucine

Product 1

HCID 18395016HCID 18395016, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of D-tert-leucine (0.250 g., 1.91 mmol, Aldrich) in dichloromethane (3 mL) and DMF (1.5 mL) was added N-methylmorpholine (0.50 mL., 4.55 mmol), followed by chlorotrimethylsilane (0.30 mL., 2.36 mmol) and the mixture stirred at room temperature for 6 hours. Diisopropylethylamine (0.300 mL., 1.72 mmol) was added, followed by 4-(4-chlorophenoxy)benzenesulfonyl chloride (0.636 g., 2.10 mmol, from example 1(c)) portionwise via a solid addition funnel. The resulting solution was then stirred at room temperature for 3.5 hours, and then partitioned between ethyl acetate and 1N aq. sodium bisulfate. The organic layer was washed with brine, dried over MgSO4, and concentrated. The residue was purified on silica gel, eluting with 40% ethyl acetate in hexane followed by 10% methanol in dichloromethane, to give N-[4-(4-chlorophenoxy)benzenesulfonyl]-D-tert-leucine as a white solid in 62% yield: mp 138-140° C.; 1H--NMR (CDCl3) δ 0.949 (s, 9H), 3.51-3.54 (d, 1H, J10.3 Hz), 5.55-5.59 (m, 1H), 6.94-7.83 (m, 8H).

Workup

  1. stirringThe resulting solution was then stirred at room temperature for 3.5 hours
  2. custompartitioned between ethyl acetate and 1N aq. sodium bisulfate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified on silica gel
  7. washeluting with 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-454e3f0fe4484484937ae3dc275ef5eb
Source dataset
uspto-grants-1999_11
Patent number
US05985900

Reaction notes

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