Hydrochloric Acid → ethyl N-(2-t-butyl-4-chloro-6-fluorobenzoxazol-7-yl)carbamate

HRID 1290623Notes

Reaction equation

HRID 1290623 reaction equation
[C:1]([C:5]1[O:6][C:7]2[C:13]([NH:14][C:15](=[O:19])[O:16][CH2:17][CH3:18])=[C:12]([F:20])[CH:11]=[CH:10][C:8]=2[N:9]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[Cl:22]N(Cl)C(OCC)=O.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CCCCCC.O.C(O)(=O)C>[C:1]([C:5]1[O:6][C:7]2[C:13]([NH:14][C:15](=[O:19])[O:16][CH2:17][CH3:18])=[C:12]([F:20])[CH:11]=[C:10]([Cl:22])[C:8]=2[N:9]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 26195N,N-DichlorourethanHCID 516892Sodium BicarbonateHCID 18916412ethyl N-(2-t-butyl-6-fluorobenzoxazol-7-yl)carbamate

Product 1

HCID 18916422ethyl N-(2-t-butyl-4-chloro-6-fluorobenzoxazol-7-yl)carbamateYield 69.3%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under a nitrogen atmosphere, a solution of 3.1 grams (11.0 mmole) of ethyl N-(2-t-butyl-6-fluorobenzoxazol-7-yl)carbamate, 35 mL of acetic acid, and 0.2 mL (2.4 mmole) of concentrated hydrochloric acid was stirred and cooled in an ice bath. During five minutes 2.2 grams (14 mmole) of N,N-dichlorourethane was added via syringe. Upon completion of the addition the reaction mixture was stirred for 4 hours, then analyzed by TLC, which indicated the reaction was complete. The reaction mixture was poured into 100 mL of water, and 15 mL of aqueous saturated sodium bicarbonate solution was carefully added. The reaction mixture was then extracted with two 75 mL portions of diethyl ether, and the combined extracts were concentrated under reduced pressure, yielding a residual oil. The oil was subjected to column chromatography on silica gel with 8:1 hexane:ethyl acetate as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 2.4 grams of ethyl N-(2-t-butyl-4-chloro-6-fluorobenzoxazol-7-yl)carbamate, m.p. 127°-129° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. temperaturecooled in an ice bath
  2. additionUpon completion of the addition the reaction mixture
  3. additionwas carefully added
  4. extractionThe reaction mixture was then extracted with two 75 mL portions of diethyl ether
  5. concentrationthe combined extracts were concentrated under reduced pressure
  6. customyielding a residual oil
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2b2b3c8010b34327bf47eae8d0a97f75
Source dataset
uspto-grants-1998_05
Patent number
US05753595

Reaction notes

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