Hydrochloric Acid → HCID 71554514, compound

HRID 2283175Notes

Reaction equation

HRID 2283175 reaction equation
[Cl:1][CH:2]([Cl:32])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][N:25]4[CH2:28][CH:27]([F:29])[CH2:26]4)=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)[O:7]C1(C)C)=[O:4].Cl.C([O-])(O)=O.[Na+]>O.O1CCOCC1>[Cl:32][CH:2]([Cl:1])[C:3]([NH:5][C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24][N:25]3[CH2:28][CH:27]([F:29])[CH2:26]3)=[CH:20][CH:19]=2)=[CH:16][CH:17]=1)[OH:7])=[O:4]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 89519257HCID 89519257, compound

Product 1

HCID 71554514HCID 71554514, compoundYield 69.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a slurry of the product of step 1 (875 mg, 1.81 mmol) in water (10 mL) is added 4 N HCl in dioxane (7 mL) and the mixture stirred at room temperature for 24 hours. Reaction is cooled with ice water and basified slowly using solid NaHCO3. The mixture is partitioned between ethylacetate and brine and subsequently extracted with ethyl acetate (3×30 mL). Combined extracts are dried over Na2SO4 and concentrated. Crude product dissolved in ethyl acetate (2 mL), adsorbed on celite and purified on silica gel eluting from 40 to 80% ethyl acetateheptane to give the title compound (560 mg). 1HNMR (400 MHz, DMSO-d6) δ: (1H-NMR) 3.07-3.20 (m, 2H), 3.49-3.61 (m, 2H), 3.66 (s, 2H), 4.14-4.32 (m, 1.5H), 4.36-4.44 (m, 0.5H), 4.54-4.60 (m, 0.5H), 4.65-4.72 (m, 0.5H), 4.85-4.91 (m, 1H), 5.07-5.14 (m, 0.5H), 5.21-5.29 (m, 0.5H), 5.95 (d, 1H, J=4.0 Hz), 6.53 (s, 1H), 7.34 (d, 1H, J=8 Hz), 7.42 (d, 1H, J=8.0 Hz), 7.57-7.63 (m, 4H), 8.61 (d, 1H, J=8 Hz), (m/z (Cl) 443 [M++1].

Workup

  1. customReaction
  2. customThe mixture is partitioned between ethylacetate and brine
  3. extractionsubsequently extracted with ethyl acetate (3×30 mL)
  4. dry with materialCombined extracts are dried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionCrude product dissolved in ethyl acetate (2 mL)
  7. custompurified on silica gel eluting from 40 to 80% ethyl acetateheptane

Sources & evidence

ORD record
ord-dfb867c96924479cb85e017ecf323ba7
Source dataset
uspto-grants-2015_09
Patent number
US09145355B2

Reaction notes

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