Methanol → HCID 66926587, compound

HRID 2404188Notes

Reaction equation

HRID 2404188 reaction equation
C[O:2][C:3]([CH:5]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[N:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:21][CH:22]4[CH2:27][CH2:26][CH:25]([C:28]([CH3:32])([CH3:31])[CH2:29][CH3:30])[CH2:24][CH2:23]4)[CH:17]=3)[N:12]=2)[CH2:6]1)=[O:4].CO.O1CCCC1.[OH-].[Li+].O>>[CH3:32][C:28]([CH:25]1[CH2:24][CH2:23][CH:22]([O:21][C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[N:12]=[C:11]([CH2:10][N:7]2[CH2:8][CH2:9][CH:5]([C:3]([OH:4])=[O:2])[CH2:6]2)[N:20]=[CH:19]3)[CH2:27][CH2:26]1)([CH3:31])[CH2:29][CH3:30]

Participants

6

Reactant 5

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 70497837HCID 70497837, compound

Product 1

HCID 66926587HCID 66926587, compoundYield 90%

Procedure

1-{6-[4-(1,1-Dimethyl-propyl)-cyclohexyloxy]-quinazolin-2-ylmethyl}-pyrrolidine-3-carboxylic acid methyl ester (229.50 mg, 5.2208E-4 mol) was dissolved in Methanol (5 mL, 0.1 mol) and Tetrahydrofuran (5 mL, 0.06 mol), followed by 2 M of Lithium hydroxide in Water (2 mL, 0.004 mol) at 23° C. for 10 minutes. Excess of solvents were removed under vacuum, and the solid residue was treated with HCl (2N, 3 mL), and extracted with DCM (20×3 mL). The organic layers were dried over Na2SO4. Removal of solvent gave a pure product (200 mg, 90%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.69-0.94 (m, 12H) 1.13-1.37 (m, 10H) 1.39-1.59 (m, 2H) 1.76-1.96 (m, 3H) 2.18-2.37 (m, 2H) 4.84 (br. s., 1H) 7.16-7.38 (m, 2H) 7.55-7.71 (m, 1H) 7.99 (br. s., 1H) MS (ESI, M+1): 426.30.

Workup

  1. customExcess of solvents were removed under vacuum
  2. additionthe solid residue was treated with HCl (2N, 3 mL)
  3. extractionextracted with DCM (20×3 mL)
  4. dry with materialThe organic layers were dried over Na2SO4
  5. customRemoval of solvent

Sources & evidence

ORD record
ord-cce27a80f7e741b0b8fd2899034a57a7
Source dataset
uspto-grants-2014_08
Patent number
US08802659B2

Reaction notes

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