Triphenylphosphine → Quinazoline

HRID 1948961Notes

Reaction equation

HRID 1948961 reaction equation
N(C(OCC)=O)=NC(OCC)=O.Cl[C:14]1[C:23]2[C:18](=[CH:19][C:20](OC)=[C:21](O)[CH:22]=2)[N:17]=[CH:16][N:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N1CCC[C@@H](O)C1)=O)(C)(C)C>ClCCl>[N:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:14]=[N:15][CH:16]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1514398(R)-1-Boc-3-hydroxypiperidineHCID 231324754-Chloro-7-methoxyquinazolin-6-ol

Product 1

HCID 9210QuinazolineYield 144.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (2.76 ml, 40% solution in toluene) was added to 4-chloro-6-hydroxy-7-methoxyquinazoline (0.89 g; prepared as described in Example 16), triphenylphosphine (1.66 g) and (3R)-1-(tert-butoxycarbonyl)-3-hydroxypiperidine (CAS Registry No 143900-43-0) (1.28 g) in dichloromethane (25 ml). The resulting solution was allowed to stir overnight at room temperature. This was purified by flash column chromatography eluting with an increasingly polar mixture of acetone/isohexane/triethylamine (79/20/1 to 64/35/1) to give 4-chloro-7-methoxy-6-[(3S)-1-(tert-butoxycarbonyl)piperidin-3-yloxy)]quinazoline as a white solid (0.794 g, 48%); Mass Spectrum: (M+H)+ 394.

Workup

  1. customThis was purified by flash column chromatography
  2. washeluting with an increasingly polar mixture of acetone/isohexane/triethylamine (79/20/1 to 64/35/1)

Sources & evidence

ORD record
ord-5542de90b32e4651a2fa4d359dfcd361
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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