Hydrochloric Acid → HCID 178450804, compound

HRID 2169379Notes

Reaction equation

HRID 2169379 reaction equation
[C:1]1([C:11]2([CH2:16][C:17]([NH2:19])=[NH:18])[CH2:15][CH2:14][CH2:13][CH2:12]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[C:21]([O:25][C:26](=[O:41])/[C:27](/O)=[C:28](\[O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)/[C:29](O)=[O:30])([CH3:24])([CH3:23])[CH3:22].C[O-].[Na+]>CO.CCCCCC.C(OCC)(=O)C>[C:21]([O:25][C:26]([C:27]1[C:28]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[C:29]([OH:30])[N:19]=[C:17]([CH2:16][C:11]2([C:1]3[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH:4]=[CH:3][CH:2]=3)[CH2:15][CH2:14][CH2:13][CH2:12]2)[N:18]=1)=[O:41])([CH3:24])([CH3:22])[CH3:23]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10942334Sodium MethoxideHCID 86725882(E)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl esterHCID 867260082-(1-Naphthalen-1-yl-cyclopentyl)-acetamidine

Product 1

HCID 178450804HCID 178450804, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-(1-naphthalen-1-yl-cyclopentyl)-acetamidine; hydrochloride (343) (4.5 g, crude) in methanol (30 mL) were added (E,Z)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester 1-methyl ester (4) (5.759 g, 18.7 mmol) and the reaction mixture was cooled to 0° C. in a ice bath. To this reaction mixture was then added sodium methoxide (25% in methanol, 10.1 mL, 46.74 mmol) and the reaction mixture was stirred at room temperature for 18 h (silica TLC, 50% ethyl acetate in hexane; Rf=0.5). The reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (50 mL) and brine (50 mL). The organic phase was thereafter dried and concentrated under vacuum to get a crude mass which was purified by CombiFlash eluted with a gradient mixture of ethyl acetate and hexane to get pure 5-benzyloxy-6-hydroxy-2-(1-naphthalen-1-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid tert-butyl ester (344) (4.1 g, 48%, 2 steps) as a brown sticky mass.

Workup

  1. washwashed with water (50 mL) and brine (50 mL)
  2. customThe organic phase was thereafter dried
  3. concentrationconcentrated under vacuum
  4. customto get a crude mass which
  5. customwas purified by CombiFlash
  6. washeluted with a gradient mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-1efd90963abd4813a6530a7d52b62aeb
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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