Hydrochloric Acid → HCID 71183725, compound

HRID 717056Notes

Reaction equation

HRID 717056 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[CH2:12]([NH:19][C@H:20]([CH2:24][OH:25])[CH:21](C)C)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.Cl.[F:60][C:61]([F:72])([F:71])[C:62]1[CH:67]=[CH:66][C:65](B(O)O)=[CH:64][CH:63]=1.C([O-])([O-])=O.[K+].[K+].[H-].[Na+]>CN(C=O)C.[Cl-].[Na+].O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:12]([N:19]1[C:7](=[O:9])[C:6]2[CH:10]=[C:2]([C:65]3[CH:66]=[CH:67][C:62]([C:61]([F:72])([F:71])[F:60])=[CH:63][CH:64]=3)[CH:3]=[CH:4][C:5]=2[O:25][CH2:24][C@@H:20]1[CH3:21])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

12

Reactant 8

HCID 313Hydrochloric Acid2×HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 27363155-Bromo-2-fluorobenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10176504benzyl(S)-valinol

Product 1

HCID 71183725HCID 71183725, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent2×

Conditions

Temperature
90 °C

Procedure

A solution of 5-bromo-2-fluorobenzoic acid (1 mmol), benzyl(S)-valinol (1 mmol), HATU (1 mmol) and diisopropylethylamine (3 mmol) in DMF (3 mL) was stirred at room temperature for 30 minutes. The reaction mixture was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated. The resided was taken up in a mixture of toluene, isopropanol and water (1 mL each) and added to a flask containing 4-trifluoromethylphenyl boronic acid (3 mmol), K2CO3 (3 mmol) and dppfPdCl2 (40 mg) under nitrogen. The reaction mixture was stirred at 90° C. for 1 h. The organic layer was separated and concentrated before being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate) to give a viscous oil. The product was dissolved in DMF (5 mL) and sodium hydride was added (5 mmol). The reaction mixture was stirred at room temperature for 40 minutes and was poured into a 1:1 solution of 1M HCl and brine and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried and concentrated before being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate) to give (S)-4-benzyl-3-methyl-7-(4-(trifluoromethyl)phenyl)-3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-one as an oil.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated sodium bicarbonate solution and brine
  3. customdried
  4. concentrationconcentrated
  5. additionThe resided was taken up in a mixture of toluene, isopropanol and water (1 mL each)
  6. additionadded to a flask
  7. customThe organic layer was separated
  8. concentrationconcentrated
  9. custombefore being purified by flash chromatography (rf=0.28 in 2:1 hexanes/ethyl acetate)
  10. customto give a viscous oil
  11. stirringThe reaction mixture was stirred at room temperature for 40 minutes
  12. extractionextracted with ethyl acetate
  13. washThe organic layer was washed with saturated sodium bicarbonate solution and brine
  14. customdried
  15. concentrationconcentrated
  16. custombefore being purified by flash chromatography (rf=0.59 in 2:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-d94e1c16147142a2a8a43503baf4f735
Source dataset
uspto-grants-2015_11
Patent number
US09193694B2

Reaction notes

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