Hydrochloric Acid → [4-Chloro-2-(3-methyl-2-oxo-butyl)-phenyl]-carbamic acid tert-butyl ester

HRID 23408Notes

Reaction equation

HRID 23408 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[CH3:15])([CH3:4])([CH3:3])[CH3:2].[Li]C(CC)C.CON(C)[C:25](=[O:29])[CH:26]([CH3:28])[CH3:27].Cl>C1COCC1.CCOCC>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=1[CH2:15][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10866371N-Methoxy-N,2-dimethylpropanamideHCID 14710386tert-Butyl (4-chloro-2-methylphenyl)carbamateHCID 178418400CID 53628100

Product 1

HCID 20756847[4-Chloro-2-(3-methyl-2-oxo-butyl)-phenyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

Following the procedure described by R. D. Clark et al. in Synthesis, 871 (1991), (4-chloro-2-methyl-phenyl)-carbamic acid tert-butyl ester (2.18 g, 9 mmole) was dissolved in anhydrous THF (30 ml) and cooled to −40° C. and s-BuLi (14.56 ml 1.3N in cyclohexane) was added slowly at such a rate to maintain the temperature below −25° C. The bright yellow solution was cooled to −50° C. and a solution of N-methoxy-N-methyl-isobutyramide (1.24 g, 9.5 mmole) in THF (5 ml) was added. The mixture was allowed to warm up to −10° C. over a 20 m period during which time the solution turned nearly colorless. Ether (50 ml) was added and the solution was poured into 1% aqueous HCl (50 ml). The aqueous layer was extracted a second time with ether (30 ml) and the combined organic extracts were washed with water and brine, dried over sodium sulfate, filtered and evaporated to dryness to afford the crude product which was purified by column chromatography (silica gel) eluting with ethyl acetate:hexane (4:1) to afford pure [4-chloro-2-(3-methyl-2-oxo-butyl)-phenyl]-carbamic acid tert-butyl ester.

Workup

  1. temperatureto maintain the temperature below −25° C
  2. temperatureThe bright yellow solution was cooled to −50° C.
  3. temperatureto warm up to −10° C. over a 20 m period during which time the solution
  4. extractionThe aqueous layer was extracted a second time with ether (30 ml)
  5. washthe combined organic extracts were washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customto afford the crude product which
  10. customwas purified by column chromatography (silica gel)
  11. washeluting with ethyl acetate:hexane (4:1)

Sources & evidence

ORD record
ord-5c5dc5b4dfd2421caebb5fb237b64db2
Source dataset
uspto-grants-2005_02
Patent number
US06852726B2

Reaction notes

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