Cloperastine Hydrochloride → (2S,4R)-1-BOC-2-hydroxyMethyl-4-aMino Pyrrolidine-HCl

HRID 1692380

Reaktionsgleichung

Reaktionsgleichung von HRID 1692380
C[O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([N:10]=[N+]=[N-])[CH2:7][N:6]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=O.C1CCN(CCOC(C2C=CC(Cl)=CC=2)C2C=CC=CC=2)CC1.Cl.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:16]([O:15][C:13]([N:6]1[CH2:7][C@H:8]([NH2:10])[CH2:9][C@H:5]1[CH2:3][OH:2])=[O:14])([CH3:19])([CH3:18])[CH3:17]

Komponenten

5

Edukt 3

HCID 161104Cloperastine HydrochlorideHCID 11369242(2S,4R)-4-Azido-1,2-pyrrolidinedicarboxylic Acid 1-(1,1-Dimethylethyl) 2-Methyl EsterHCID 21226445Aluminium lithium hydride

Produkt 1

HCID 45072313(2S,4R)-1-BOC-2-hydroxyMethyl-4-aMino Pyrrolidine-HCl

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of (2S,4R)-4-azido-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester [Marusawa, H.; Setoi, H.; Sawada, A.; Kuroda, A.; Seki, J.; Motoyama, Y.; Tanaka, H. Bioorganic & Medicinal Chemistry (2002), 10(5), 1399-1415] (1.0 g, 4 mmol) in THF (5 ml) was added to an ice-cooled suspension of LAH (0.6 g, 15 mmol) in THF (5 ml) under Ar. The reaction was stirred for 1 h after which time it was quenched by cautious addition of water. The resulting precipitate was filtered, rinsed with EtOAc and the organics concentrated. The crude (2S,4R)-4-amino-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.7 g, 3 mmol) thus obtained was then dissolved in CH2Cl2 (15 ml), saturated NaHCO3 (15 ml) was added followed by acetic anhydride (0.3 ml, 3 mmol) and the mixture stirred for 2 h. The reaction mixture was then separated, the organic phase dried (Na2SO4) and concentrated affording crude (2S,4R)-4-acetylamino-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.62 g, 79%). Treatment of this with a 4 N solution of hydrochloric acid in dioxane afforded the title product (0.5 g, quant) as a yellow powder. MS: 159.1 (MH+).

Aufarbeitung

  1. temperaturecooled
  2. customwas quenched by cautious addition of water
  3. filtrationThe resulting precipitate was filtered
  4. washrinsed with EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-dd35224282894a4195af3a5f320f7940
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153805B2

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