Triphenylphosphine → (R)-3-(5-Cyano-2-oxo-2H-pyridin-1-yl)-pyrrolidine-1-carboxylic acid 5-hydroxy-adamantan-2-yl ester

HRID 1752328Notes

Reaction equation

HRID 1752328 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[OH:13][C:14]12[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:22][CH:16]([CH:17]3[O:24][C:25]([N:27]3[CH2:31][CH2:30][C@H:29](O)[CH2:28]3)=[O:26])[CH2:15]1)[CH2:21]2.[O:33]=[C:34]1[NH:39][CH:38]=[C:37]([C:40]#[N:41])[CH:36]=[CH:35]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[OH:13][C:14]12[CH2:23][CH:18]3[CH2:19][CH:20]([CH2:22][CH:16]([CH:17]3[O:24][C:25]([N:27]3[CH2:31][CH2:30][C@@H:29]([N:39]4[CH:38]=[C:37]([C:40]#[N:41])[CH:36]=[CH:35][C:34]4=[O:33])[CH2:28]3)=[O:26])[CH2:15]1)[CH2:21]2

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 70621976-HydroxynicotinonitrileHCID 58171511(S)-3-hydroxy-pyrrolidine-1-carboxylic acid 5-hydroxy-adamantan-2-yl ester

Product 1

HCID 58171561(R)-3-(5-Cyano-2-oxo-2H-pyridin-1-yl)-pyrrolidine-1-carboxylic acid 5-hydroxy-adamantan-2-yl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diethyl azodicarboxylate (40% in toluene, 1.7 mL) is added to a mixture of (S)-3-hydroxy-pyrrolidine-1-carboxylic acid 5-hydroxy-adamantan-2-yl ester (ca. 1:1 mixture of cis- and trans-isomer, 0.50 g), 6-oxo-1,6-dihydro-pyridine-3-carbonitrile (0.22 g), triphenylphosphine (0.97 g), and tetrahydrofuran (10 ml) at room temperature. The resulting mixture is stirred for 2 h and then concentrated. The residue is chromatographed on silica gel (ethyl acetate/methanol 95:5→80:20) and then on reversed phase (HPLC, acetonitrile/water containing 1.36% trifluoroacetic acid) to give the title compound as a mixture of two diastereomers (cis/trans ca. 1:1). Yield: 8 mg (1% of theory); LC (method 1): tR=1.03/1.06 min; Mass spectrum (ESI+): m/z=384 [M+H]+.

Workup

  1. concentrationconcentrated
  2. customThe residue is chromatographed on silica gel (ethyl acetate/methanol 95:5→80:20)

Sources & evidence

ORD record
ord-0be09ef9d3f64dbdb2f9330cac0df3d8
Source dataset
uspto-grants-2015_10
Patent number
US09163012B2

Reaction notes

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