Sodium Methoxide → HCID 178450811, compound

HRID 2169359Notes

Reaction equation

HRID 2169359 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:13][C:14]([NH2:16])=[NH:15])[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl.C1(C2(CC(N)=N)CCCC2)C=CC=CC=1.[C:33]([O:37][C:38](=[O:53])/[C:39](/O)=[C:40](\[O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)/[C:41](O)=[O:42])([CH3:36])([CH3:35])[CH3:34].C[O-].[Na+]>CO.C(OCC)(=O)C.CCCCCC>[C:33]([O:37][C:38]([C:39]1[C:40]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[C:41]([OH:42])[N:16]=[C:14]([CH2:13][C:8]2([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH2:12][CH2:11][CH2:10][CH2:9]2)[N:15]=1)=[O:53])([CH3:36])([CH3:34])[CH3:35]

Participants

8

Reactant 4

HCID 10942334Sodium MethoxideHCID 867258072-(1-Phenyl-cyclopentyl)-acetamidine HCl saltHCID 867258102-[1-(4-Chlorophenyl)-cyclopentyl]-acetamidineHCID 86725882(E)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester

Product 1

HCID 178450811HCID 178450811, compoundYield 91%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-[1-(4-chlorophenyl)-cyclopentyl]-acetamidine; hydrochloride (322) (3.1 g, 11.34 mmol) in methanol (25 mL) was added (E,Z)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester 1-methyl ester (4) (4.19 g, 13.61 mmol) and cooled to 0° C. To this reaction mixture was then added sodium methoxide (25% in methanol) (7.4 mL, 34.03 mmol) and stirred at room temperature for 16 h (TLC; ethyl acetate:hexane=1:1, Rf=0.5). The reaction mixture was diluted with ethyl acetate (300 mL), washed with water (60 mL) and brine (60 mL) and dried and concentrated in vacuo to get crude mass which was purified by CombiFlash eluted with gradient polarity mobile phase (hexane to 50% ethyl acetate in hexane) to get pure 5-benzyloxy-2-[1-(4-chlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid tert-butyl ester (323) (5.1 g, 91%) as a light brown solid.

Workup

  1. washwashed with water (60 mL) and brine (60 mL)
  2. customdried
  3. concentrationconcentrated in vacuo
  4. customto get crude mass which
  5. customwas purified by CombiFlash
  6. washeluted with gradient polarity mobile phase (hexane to 50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-484d261894284809ab340e823713ac9f
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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