Hexachloroethane → tert-butyl [(1S)-2-{[5-fluoro-6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate

HRID 1026347Notes

Reaction equation

HRID 1026347 reaction equation
C(N(CC)CC)C.ClC(Cl)(Cl)C(Cl)(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:35][C:36]1[CH:41]=[C:40]([OH:42])[CH:39]=[CH:38][C:37]=1[NH:43][C:44]([C:46]1[N:51]=[CH:50][C:49]([O:52][CH2:53][C@@H:54]([NH:56][C:57](=[O:63])[O:58][C:59]([CH3:62])([CH3:61])[CH3:60])[CH3:55])=[CH:48][C:47]=1[F:64])=O>C(#N)C.O>[F:64][C:47]1[CH:48]=[C:49]([O:52][CH2:53][C@@H:54]([NH:56][C:57](=[O:63])[O:58][C:59]([CH3:61])([CH3:60])[CH3:62])[CH3:55])[CH:50]=[N:51][C:46]=1[C:44]1[O:35][C:36]2[CH:41]=[C:40]([OH:42])[CH:39]=[CH:38][C:37]=2[N:43]=1

Participants

7

Reactant 4

HCID 6214HexachloroethaneHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86666268tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]-5-fluoropyridin-3-yl}oxy)-1-methylethyl]carbamate

Product 1

HCID 136372365tert-butyl [(1S)-2-{[5-fluoro-6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

A mixture of 5-({(2S)-2-[(tert-butoxycarbonyl)amino]propyl}oxy)-3-fluoropyridine-2-carboxylic acid (5.00 g), 4-aminobenzene-1,3-diol hydrochloride (2.57 g), HATU (6.05 g), N,N-diisopropylethylamine (5.56 mL), and DMF (50 mL) was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]-5-fluoropyridin-3-yl}oxy)-1-methylethyl]carbamate (2.51 g) as a mixture with impurities. Triethylamine (6.64 mL) was added to a solution of hexachloroethane (3.53 g) and triphenylphosphine (4.69 g) in acetonitrile (25 mL) at room temperature. The mixture was stirred at room temperature for 10 min. Then a mixture of tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]-5-fluoropyridin-3-yl}oxy)-1-methylethyl]carbamate (2.51 g, a mixture with impurities) and acetonitrile (25 mL) was added, and the mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (0.770 g) as a pale yellow solid.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d6c0c79ef4f3407a9b5a1ad624dddf50
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

Loading…