Water → tert-butyl(R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate

HRID 2406167Notes

Reaction equation

HRID 2406167 reaction equation
[C:1]([C@@H]1CCN(N)C1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH2:14]([N:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[CH3:15].ClC1C2[C:26](=[CH:27][C:28]([CH3:32])=[CH:29][CH:30]=2)[N:25]=[C:24]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[OH:39])[N:23]=1.O.C[N:42](C=O)C>C(Cl)Cl>[OH:39][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[C:24]1[N:23]=[C:14]([N:16]2[CH2:19][CH2:20][C@@H:18]([NH:42][C:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[CH2:17]2)[C:15]2[C:26](=[CH:27][C:28]([CH3:32])=[CH:29][CH:30]=2)[N:25]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 66616410(R)-3-Boc-aminopyrrolidineHCID 1361050322-(4-Chloro-7-methylquinazolin-2-yl)-phenol

Product 1

HCID 136121326tert-butyl(R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamateYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled (0-5° C.) solution of (3R)-(+)-3-Boc-aminopyrrolidine (12.0 g, 65 mmol) and triethylamine (19 mL, 129 mmol) in DMF (100 mL) was added a solution of 2-(4-chloro-7-methylquinazolin-2-yl)phenol (17.4 g, 64 mmol) in CH2Cl2 (500 mL) and DMF (100 mL). After stirring the mixture for 5 hours at room temperature, water (900 mL) was added. The aqueous layer was extracted with dichloromethane (3×300 mL), and the combined organic layers were washed with saturated aqueous NaCl solution (300 mL), dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The yellow residue (21 g) was treated with 100 mL methanol at room temperature. The solid was collected by filtration and was washed with methanol to yield tert-butyl (R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (15.1 g, 55%) as a yellow solid.

Workup

  1. extractionThe aqueous layer was extracted with dichloromethane (3×300 mL)
  2. washthe combined organic layers were washed with saturated aqueous NaCl solution (300 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness under reduced pressure
  6. additionThe yellow residue (21 g) was treated with 100 mL methanol at room temperature
  7. filtrationThe solid was collected by filtration
  8. washwas washed with methanol

Sources & evidence

ORD record
ord-b8cbc46faa0a4e42ba152bd4979571d9
Source dataset
uspto-grants-2014_08
Patent number
US08809353B2

Reaction notes

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