Hydrochloric Acid → HCID 67175712, compound

HRID 2355291Notes

Reaction equation

HRID 2355291 reaction equation
[OH:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[C:6]([OH:12])[CH:5]=[CH:4][C:3]=1[C:13](=[O:17])[CH:14]([CH3:16])[CH3:15].C(OC(=O)[NH:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32]O)=[CH:28][CH:27]=1)(C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[ClH:68].O1CCOCC1>C1(C)C=CC=CC=1>[ClH:68].[NH2:24][CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][O:12][C:6]2[CH:5]=[CH:4][C:3]([C:13](=[O:17])[CH:14]([CH3:15])[CH3:16])=[C:2]([OH:1])[C:7]=2[C:8]([F:9])([F:10])[F:11])=[CH:28][CH:27]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2794813tert-Butyl [4-(hydroxymethyl)benzyl]carbamateHCID 534139691-[2,4-Dihydroxy-3-(trifluoromethyl)phenyl]-2-methylpropan-1-one

Product 1

HCID 67175712HCID 67175712, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Mechanically stir solutions of 1-(2,4-dihydroxy-3-trifluoromethyl-phenyl)-2-methyl-propan-1-one (211 g, 850.1 mmol), (4-hydroxymethyl-benzyl)-carbamic acid tert-butyl ester (195 g, 821.8 mmol), and triphenylphosphine (212 g; 808.3 mmol) in toluene (9 L) in two separate 22-L Morton flasks. Treat solutions with diisopropyl azodicarboxylate (183 mL, 923 mmol) over a 60 min period, then stir over the weekend at room temperature. Combine the solutions and evaporate to a brown oil. Dissolve the oil in 1,4-dioxane (8 L), treat with 4N hydrogen chloride solution in 1,4-dioxane (3 L, 12 mole), and heat to 92° C. for 6 hrs (out-gassing and precipitation is observed at 52° C. during the warm up period). Cool to room temperature, filter the resulting solid and wash with dioxane, 30% dioxane in hexanes, and hexanes to provide the title compound (510 g, 78% yield) as a tan solid. HPLC Rt=4.71 min; 1H NMR (DMSO-d6) δ 14.00 (s, 1H), 8.4 (bs, 3H), 7.50 (ABq, J=12.0, 8.0 Hz, 4H), 6.92 (d, J=8.0 Hz, 1H), 5.37 (s, 2H), 4.0 (m, 2H), 3.73 (hept, J=4.0 Hz, 1H), 1.12 (d, J=4.0 Hz, 6H); 19F NMR (DMSO-d6) δ-54.10; MS (m/z): 368.0 (M+1).

Workup

  1. customevaporate to a brown oil
  2. dissolutionDissolve the oil in 1,4-dioxane (8 L)
  3. temperatureheat to 92° C. for 6 hrs (out-gassing and
  4. customprecipitation
  5. customis observed at 52° C.
  6. temperaturewarm up period)
  7. temperatureCool to room temperature
  8. filtrationfilter the resulting solid
  9. washwash with dioxane, 30% dioxane in hexanes, and hexanes

Sources & evidence

ORD record
ord-6df94d2500aa41058496c53894aa175a
Source dataset
uspto-grants-2010_07
Patent number
US07754742B2

Reaction notes

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