Benzhydrylamine → methyl 3-[N-(diphenylmethyl) aminosulfonyl]-2(R)-methylpropionate

HRID 1593702Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1593702
[NH2:1][CH:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.Cl[S:23]([CH2:26][C@H:27]([CH3:32])[C:28]([O:30][CH3:31])=[O:29])(=[O:25])=[O:24]>C(Cl)Cl>[C:9]1([CH:2]([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[NH:1][S:23]([CH2:26][C@H:27]([CH3:32])[C:28]([O:30][CH3:31])=[O:29])(=[O:25])=[O:24])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Komponenten

5

Edukt 3

HCID 7036BenzhydrylamineHCID 8471TriethylamineHCID 18738451methyl 3-chlorosulfonyl-2(R)-methylpropionate

Produkt 1

HCID 18738453methyl 3-[N-(diphenylmethyl) aminosulfonyl]-2(R)-methylpropionateAusbeute 66,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A 100 mL round bottom flask equipped with magnetic stir bar was charged with 1 g aminodiphenylmethane, 2 mL triethylamine in 20 mL CH2Cl2. The reaction was cooled to 0° C. and 1 g of methyl 3-chlorosulfonyl-2(R)-methylpropionate was slowly added. The reaction was stirred 1 hour then concentrated in vacuo. The residue was partioned between ethyl acetate and water. The organic phase was washed with brine, dried, and concentrated in vacuo. Trituration from Et2O/hexanes gave 1.15 g of methyl 3-[N-(diphenylmethyl)aminosulfonyl]-2(R)-methylpropionate as a white solid. HRMS (M+Li): calcd. 354.1351, obs 354.1569. Part B: methyl 3-[N-(benzyl)-N-(diphenylmethyl)aminosulfonyl]-2(R)-methylpropionate A 100 mL round bottom flask equipped with magnetic stir bar and N2 inlet was charged with 1.11 g of methyl 3-[N-(diphenylmethyl)aminosulfonyl]-2(R)-methylpropionate, 447 mg K2CO3, 347 mL benzyl bromide in 20 mL DMF. The reaction was stirred overnight, concentrated in vacuo and partioned between ethyl acetate and water. The organic phase was washed with brine, dried and concentrated in vacuo to 1.2 g of a clear oil. Flash chromatography on silica gel (30% ethyl acetate/hexanes) afforded 730 mg of methyl 3-[N-(benzyl)-N-(diphenylmethyl)aminosulfonyl]-2(R)-methylpropionate. HRMS (M+Li): calcd. 444.1821, obs 444.1865. Part C: 3-[N-(benzyl)-N-(diphenylmethyl)aminosulfonyl]-2(R)-methylpropionic acid A 50 mL round bottom flask equipped with magnetic stir bar was charged with 320 mg of methyl 3-[N-(benzyl)-N-(diphenylmethyl)aminosulfonyl]-2(R)-methylpropionate and 120 mg LiOH (4 eq) in 4 mL 50% aq THF. After 5 minutes 2 mL MeOH added to get homogeneous solution, after 1 hour the reaction was partioned between ethyl acetate and 5% aq KHSO4. The organic phase was washed with brine, dried, and concentrated in vacuo to yield 250 mg of 3-[N-(benzyl)-N-(diphenylmethyl)aminosulfonyl]-2(R)-methylpropionic acid as a clear semi-solid. HRMS (M+Li): calcd. 430.1664, obs. 430.1698.

Aufarbeitung

  1. customA 100 mL round bottom flask equipped with magnetic stir bar
  2. concentrationthen concentrated in vacuo
  3. washThe organic phase was washed with brine
  4. customdried
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-68404b3ea33f4b598892011442a1fb27
Quelldatensatz
uspto-grants-2007_11
Patentnummer
US07297793B2

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