Sodium Hydroxide → HCID 59729996, compound

HRID 130816Notes

Reaction equation

HRID 130816 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:21]1[N:29]=[CH:28][CH:27]=[CH:26][C:22]=1[C:23]([NH2:25])=[O:24].[OH-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:17])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:21]2[C:22]([C:23](=[O:24])[NH2:25])=[CH:26][CH:27]=[CH:28][N:29]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 825882-ChloronicotinamideHCID 11831452tert-butyl N-(2-(4-hydroxyphenyl)ethyl)carbamate

Product 1

HCID 59729996HCID 59729996, compoundYield 71.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Dissolve [2-(4-hydroxyphenyl)ethyl]carbamic acid tert-butyl ester (Example 377, Part A) (0.500 g, 2.11 mmol) in DMF (10.5 mL). Add NaH (80% in mineral oil) (0.070 g, 2.32 mmol). Stir at room temperature for 30 minutes. Add 2-chloronicotinamide (0.330 g, 2.11 mmol) and heat to 100° C. Remove DMF as an azeotrope with xylenes after 18¾ hours. Take the solid up with ethyl acetate (150 mL) and 1.0 N NaOH (75 mL). Separate the two layers. Extract the aqueous layer with ethyl acetate (1×150 mL). Wash the combined organic layers with brine (1×50 mL), dry over Na2SO4, filter and concentrate. Purify by flash chromatography, eluting with 35-45% ethyl acetate in dichloromethane to give the title compound (0.538 g, 71.4%): MS ES+ 358.3 (M+H)+, base peak ES+ 302.1 (M+2H—C(CH3)3)+, MS ES− 356.4 (M−H)−; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 50-99% over 19 min], tR=12.9 min, 100% purity.

Workup

  1. customSeparate the two layers
  2. extractionExtract the aqueous layer with ethyl acetate (1×150 mL)
  3. washWash the combined organic layers with brine (1×50 mL)
  4. dry with materialdry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by flash chromatography
  8. washeluting with 35-45% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-f2b037f7f4e2496386cb281f34952d8d
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

Loading…