Hydrochloric Acid → Tert-butyl 3-{3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl}-3-hydroxypentanoate

HRID 1826849Notes

Reaction equation

HRID 1826849 reaction equation
Br[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].Cl.[CH2:11]([O:18][CH2:19][C:20]1[C:21]([O:30][CH3:31])=[N:22][CH:23]=[CH:24][C:25]=1[C:26](=[O:29])[CH2:27][CH3:28])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Cl-].[NH4+]>O1CCCC1.[Zn]>[CH2:11]([O:18][CH2:19][C:20]1[C:21]([O:30][CH3:31])=[N:22][CH:23]=[CH:24][C:25]=1[C:26]([OH:29])([CH2:27][CH3:28])[CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 79177tert-Butyl bromoacetateHCID 105411281-(3-Benzyloxymethyl-2-methoxy-pyridin-4-yl)-propan-1-one

Product 1

HCID 10834902Tert-butyl 3-{3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl}-3-hydroxypentanoateYield 95%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

tert-butyl bromoacetate (13 ml, 80 mmol) is added dropwise to a zinc suspension (5.3 g, 80 mmol activated with 6N HCl over 10 seconds, then washed successively with water until a neutral pH is achieved, with acetone and with diethyl ether) in anhydrous tetrahydrofuran (60 ml) under reflux. The reaction medium is maintained under reflux for another 10 minutes after the addition is terminated. Then, a solution of 1-{3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl}-1-propanone (5.8 g, 20 mmol) in anhydrous tetrahydrofuran (20 ml) is added and the reaction mixture is agitated under reflux for another hour. The reaction is stopped at 0° C. with saturated aqueous ammonium chloride (100 ml) and the reaction mixture is extracted with diethyl ether. The combined extracts are dried over sodium sulphate and evaporated, which produces a yellow oil which is purified by column chromatography (SiO2, TBMO/HX: 5/95 to 10/90) in order to obtain the tert-butyl ester (J) (7 g, 95%) in the form of a limpid liquid.

Workup

  1. washwashed successively with water until a neutral pH
  2. temperatureunder reflux
  3. temperatureThe reaction medium is maintained
  4. temperatureunder reflux for another 10 minutes
  5. additionafter the addition
  6. customis terminated
  7. temperatureunder reflux for another hour
  8. extractionthe reaction mixture is extracted with diethyl ether
  9. dry with materialThe combined extracts are dried over sodium sulphate
  10. customevaporated
  11. customwhich produces a yellow oil which
  12. customis purified by column chromatography (SiO2, TBMO/HX: 5/95 to 10/90) in order

Sources & evidence

ORD record
ord-eb0c82f05d80488987a897c820b9198c
Source dataset
uspto-grants-2006_05
Patent number
US07053102B2

Reaction notes

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