Hydrochloric Acid → HCID 89408384, compound

HRID 516210Notes

Reaction equation

HRID 516210 reaction equation
[C:1]1([O:7][C:8](=[O:22])[NH:9][C@@H:10]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([Cl:20])[C:15]=2[F:21])[CH2:11][CH:12]=C)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Mg]Br)C=C.ClC1C(F)=C([C@H](N[S@@](C(C)(C)C)=[O:42])CC=C)C=CN=1.ClC1C(F)=C([C@@H](N[S@@](C(C)(C)C)=O)CC=C)C=CN=1.Cl.O1CCOCC1>C1COCC1.CO>[Cl:20][C:16]1[C:15]([F:21])=[C:14]([C@H:10]([NH:9][C:8](=[O:22])[O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:11][CH:12]=[O:42])[CH:19]=[CH:18][N:17]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86721099HCID 86721099, compoundHCID 86721100HCID 86721100, compoundHCID 86721101HCID 86721101, compoundHCID 178455850HCID 178455850, compound

Product 1

HCID 89408384HCID 89408384, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(R)-Phenyl(1-(2-chloro-3-fluoropyridin-4-yl)but-3-en-1-yl)carbamate: To a solution of Intermediate 24A (1.13 g, 4.30 mmol) in THF (50 mL) at was −78° C. was added allylmagnesium bromide (1 M in ether) (8 mL, 8.00 mmol). The reaction was stirred at −78° C. for 0.5 h and warmed up to rt. The mixture was stirred for 1 h at rt and quenched with saturated NH4Cl. The mixture was extracted with EtOAc (3×). The combined organic layer was concentrated to give a 5:1 mixture of (R)-N-((R)-1-(2-chloro-3-fluoropyridin-4-yl)but-3-en-1-yl)-2-methylpropane-2-sulfinamide and (R)—N-((5)-1-(2-chloro-3-fluoropyridin-4-yl)but-3-en-1-yl)-2-methylpropane-2-sulfinamide (1.56 g, 119%) as an orange oil. The oil was taken up with methanol (10.00 mL) and treated with 4 N HCl in dioxane (3 mL, 99 mmol). The reaction was stirred at rt for 1.5 h and then concentrated to give the desired product (0.55 g, 40%) as an orange oil. MS (ESI) m/z: 321.1 (M+H)+.

Workup

  1. customat was −78° C.
  2. temperaturewarmed up to rt
  3. stirringThe mixture was stirred for 1 h at rt
  4. customquenched with saturated NH4Cl
  5. extractionThe mixture was extracted with EtOAc (3×)
  6. concentrationThe combined organic layer was concentrated
  7. customto give
  8. stirringThe reaction was stirred at rt for 1.5 h
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-43e7e39c33a24fcabb1ca813e80aff7b
Source dataset
uspto-grants-2015_08
Patent number
US09108981B2

Reaction notes

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