Triphenylphosphine → tert-butyl(2R)-2-{[(7-(benzyloxy)-3-{[(2,2-dimethylpropanoyl)oxy]methyl}-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate

HRID 640012Notes

Reaction equation

HRID 640012 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[C:15]([O:21][CH2:22][N:23]1[C:32](=[O:33])[C:31]2[C:26](=[CH:27][C:28]([O:35][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:29][C:30]=2O)[N:25]=[CH:24]1)(=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C>ClCCl>[CH2:36]([O:35][C:28]1[CH:27]=[C:26]2[C:31]([C:32](=[O:33])[N:23]([CH2:22][O:21][C:15](=[O:20])[C:16]([CH3:17])([CH3:18])[CH3:19])[CH:24]=[N:25]2)=[C:30]([O:1][CH2:2][C@H:3]2[CH2:7][CH2:6][CH2:5][N:4]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:29]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 688279N-(tert-Butoxycarbonyl)-D-prolinolHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 119746277-Benzyloxy-5-hydroxy-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-one

Product 1

HCID 69638708tert-butyl(2R)-2-{[(7-(benzyloxy)-3-{[(2,2-dimethylpropanoyl)oxy]methyl}-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylateYield 36%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

tert-butyl (2R)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (1.70 g, 8.6 mmol) was added to a solution of [7-(benzyloxy)-5-hydroxy-4-oxoquinazolin-3(4H)-yl]methyl pivalate (see WO01/094341, 3.0 g, 7.8 mmol) and PS-triphenylphosphine (1.5 mmol/g, 7.2 g, 4.2 mmol) in dichloromethane (120 ml). The reaction mixture was cooled to 0° C. and then a solution of di-tert-butylazodicarboxylate (2.1 g, 9.3 mmol) in dichloromethane (15 ml) was added dropwise over 30 minutes. The mixture was allowed to warn to room temperature and then stirred for 2 hours. The mixture was evaporated under reduced pressure and the residue was purified by silica gel chromatography eluting with a 0 to 10% mixture methanol in dichloromethane to give tert-butyl (2R)-2-{[(7-(benzyloxy)-3-{[(2,2-dimethylpropanoyl)oxy]methyl}-4-oxo-3,4-dihydroquinazolin-5-yl)oxy]methyl}pyrrolidine-1-carboxylate (1.58 g, 36% yield):

Workup

  1. customto warn to room temperature
  2. customThe mixture was evaporated under reduced pressure
  3. customthe residue was purified by silica gel chromatography
  4. washeluting with a 0 to 10% mixture methanol in dichloromethane

Sources & evidence

ORD record
ord-e334c83670404150ae96ddc591484d70
Source dataset
uspto-grants-2010_04
Patent number
US07691867B2

Reaction notes

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