Hydrochloric Acid → (R)-methyl 3-(tert-butyldimethylsilyloxy)-4-chlorobutanoate

HRID 1855232Notes

Reaction equation

HRID 1855232 reaction equation
[Cl:1][CH2:2][C@H:3]([OH:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6].[C:10]([Si:14](Cl)([CH3:16])[CH3:15])([CH3:13])([CH3:12])[CH3:11].N1C=CN=C1.Cl>C(Cl)Cl.CN(C1C=CN=CC=1)C.O>[Si:14]([O:9][C@@H:3]([CH2:2][Cl:1])[CH2:4][C:5]([O:7][CH3:8])=[O:6])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 10920707Methyl (R)-4-Chloro-3-hydroxybutyrate

Product 1

HCID 58048499(R)-methyl 3-(tert-butyldimethylsilyloxy)-4-chlorobutanoateYield 113.9%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-methyl 4-chloro-3-hydroxybutanoate (15 g, 98.7 mmol) in CH2Cl2 (240 mL) was stirred overnight with tert-butyl-chloro-dimethyl-silane (17.82 g, 118.2 mmol), imidazole (33.6 g, 493.5 mmol) and a catalytic amount of DMAP (0.6 g, 4.92 mmol) at room temperature under N2. The reaction mixture was poured into water (150 mL) and acidified to pH 6-7 by dropwise addition of cold aqueous HCl (0.5 M). The aqueous phase was extracted with CH2Cl2 (3×60 mL). The combined organic phases were washed with sat. Na2CO3 solution, brine, dried over anhydrous Na2SO4 and concentrated to give (R)-methyl 3-(tert-butyldimethylsilyloxy)-4-chlorobutanoate (30 g, crude).

Workup

  1. customat room temperature
  2. extractionThe aqueous phase was extracted with CH2Cl2 (3×60 mL)
  3. washThe combined organic phases were washed with sat. Na2CO3 solution, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-5c3dabe240144836bdf96c3de84466d2
Source dataset
uspto-grants-2015_02
Patent number
US08962856B2

Reaction notes

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