Triphenylphosphine → Quinazoline

HRID 1175077Notes

Reaction equation

HRID 1175077 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 1514399tert-butyl (3S)-3-hydroxypiperidine-1-carboxylateHCID 231324754-Chloro-7-methoxyquinazolin-6-ol

Product 1

HCID 9210QuinazolineYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

Diethyl azodicarboxylate (5.7 ml) was added to 4-chloro-6-hydroxy-7-methoxyquinazoline (4.39 g; prepared as described in Example 1 (Preparation of starting materials)), triphenylphosphine (8.2 g) and (3S)-1-(tert-butoxycarbonyl)-3-hydroxypiperidine (Commercially Available—CAS Registry No 14390044-1) (6.29 g) in dichloromethane (130 ml) and the reaction mixture was stirred at 40° C. for 6 hours. This was allowed to stand overnight at −18° C. then filtered. The filtrates were purified by flash column chromatography eluting with acetone/isohexane/triethylamine (17/82/1) to give 4-chloro-7-methoxy-6-[(3R)-1-(tert-butoxycarbonyl)piperidin-3-yloxy)]quinazoline as a white solid (0.794 g, 48%); Mass Spectrum: (M+H)+394.

Workup

  1. waitto stand overnight at −18° C.
  2. filtrationthen filtered
  3. customThe filtrates were purified by flash column chromatography
  4. washeluting with acetone/isohexane/triethylamine (17/82/1)

Sources & evidence

ORD record
ord-7ccba3bb0ccd4944967d345919e33e6d
Source dataset
uspto-grants-2010_11
Patent number
US07838530B2

Reaction notes

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