Hydrochloric Acid → (S)-3-Methyl-1-(pyridin-2-yl)butan-1-amine

HRID 874740Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 874740
[ClH:1].[CH:2]1([C@@H:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[NH:8]S(C(C)(C)C)=O)[CH2:6][CH2:5][CH2:4][CH2:3]1.[CH3:21]O>>[ClH:1].[CH:2]1([C@H:7]([NH2:8])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[CH2:3][CH2:4][CH2:5][CH2:6]1.[CH3:21][CH:6]([CH3:5])[CH2:2][C@@H:7]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1)[NH2:8]

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 86706883(RS)-N-((S)-Cyclopentyl(pyridin-2-yl)methyl)-2-methylpropane-2-sulfinamide

Produkt 2

HCID 86306748(S)-3-Methyl-1-(pyridin-2-yl)butan-1-amineHCID 86706884(S)-Cyclopentyl(pyridin-2-yl)methanamine hydrochloride

Versuchsvorschrift

The title compound was synthesized according to General Method I utilizing HCl (2.0 M in Et2O, 31.4 mL, 62.8 mmol) and a solution of (RS)—N-((S)-cyclopentyl(pyridin-2-yl)methyl)-2-methylpropane-2-sulfinamide (8.8 g, 31.4 mmol) in MeOH (100 mL). After the addition was complete the cooling bath was removed and the mixture was stirred at rt for 1 h. The reaction mixture was concentrated under reduced pressure and the residue was suspended in Et2O (125 mL). The precipitation was filtered off and washed with Et2O (2×125 mL) and dried under reduced pressure yielding the crude product (7.7 g, 95.0% ee (S)) as a white solid. The crude product was recrystallised from t-BuOMe (150 mL), EtOH (200 mL) and MeOH (170 mL) at 80° C. The crystals formed after the solution cooled down were collected by filtration (3.3 g, 99.0% ee (S)) and the filtrate was concentrated under reduced pressure and was recrystallised again from t-BuOMe (100 mL) and MeOH (150 mL). The second crop of crystals were collected by filtration (1.3 g, 98.0% ee (S)) resulting in a combined yield of 4.6 g, 69% isolated yield). 1H NMR (400 MHz, D2O+NaOH) δ ppm 8.81 (d, J=5.5 Hz, 1H), 8.55 (t, J=8.0 Hz, 1H), 8.06 (d, J=8.0 Hz, 1H), 7.99 (t, J=6.5 Hz, 1H), 4.53 (d, J=10.5 Hz, 1H), 2.63-2.50 (m, 1H), 2.11-2.01 (m, 1H), 1.84-1.40 (m, 6H), 1.24-1.12 (m, 1H). The ee of the compound was determined by acetylating small samples with AcCl (see example below for the synthesis) and analysing the products, (S)— and (R)—N-(Cyclopentyl(pyridin-2-yl)methyl)acetamides, by chiral HPLC: Daicel Chiralpak AD-H, 80:20 v/v heptane-EtOH (+0.2% Et3N), 1.0 mL/min, λ=230 nm, Rt=9.5 min (R), Rt=25.4 min (S).

Aufarbeitung

  1. additionAfter the addition
  2. customwas removed
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customThe precipitation
  5. filtrationwas filtered off
  6. washwashed with Et2O (2×125 mL)
  7. customdried under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-d5e9b7be12334d6cbee27947dfe33bfb
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08980934B2

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