Acetic Acid → (2R,3R)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsiloxy)-2-[(3-chloro-4-cyano-2-methylphenylamino)methyl]pyrrolidine

HRID 501592

Reaktionsgleichung

Reaktionsgleichung von HRID 501592
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH:21]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([Cl:32])[C:25]=1[CH3:33].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>CN(C=O)C.C(Cl)Cl.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH2:21][NH:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([Cl:32])[C:25]=1[CH3:33])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Komponenten

8

Edukt 4

HCID 176Acetic Acid2×HCID 5049666Sodium triacetoxyborohydride2×HCID 16732142tert-Butyl-(2S,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-2-formylpyrrolidine-1-carboxylateHCID 218754134-Amino-2-chloro-3-methylbenzonitrile

Produkt 1

HCID 59424841(2R,3R)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsiloxy)-2-[(3-chloro-4-cyano-2-methylphenylamino)methyl]pyrrolidineAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of (2S,3R)-3-(tert-Butyldimethylsilanyloxy)-2-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester (51C) (661 mg, 2.0 mmol) in 5% DMF in CH2Cl2 (10 mL) at rt was added 4-amino-2-chloro-3-methyl-benzonitrile (340 mg, 2.04 mmol) followed by NaBH(OAc)3 (636 mg, 3.0 mmol) and HOAc (180 μL, 3 mmol). The reaction was stirred under nitrogen at rt for 18 h. Additional portions of NaBH(OAc)3 (424 mg, 2.0 mmol) and HOAc (120 μL, 2 mmol) were added, and the reaction was stirred for an additional 18 h. The reaction was diluted with EtOAc (50 mL) and the organic layer was washed with saturated aqueous NaHCO3 (50 ml), dried (MgSO4), filtered and concentrated. Purification via flash chromatography (silica gel, 0 to 15% EtOAc/hexanes) provided the title compound (605 mg, 1.26 mmol, 63%). MS m/z 480 [M+H]+.

Aufarbeitung

  1. stirringthe reaction was stirred for an additional 18 h
  2. washthe organic layer was washed with saturated aqueous NaHCO3 (50 ml)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via flash chromatography (silica gel, 0 to 15% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-182c28df328b40b69754c4df7d5a5fb1
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07772267B2

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