Hydrochloric Acid → Milveterol

HRID 226284Notes

Reaction equation

HRID 226284 reaction equation
[OH:1][C@H:2]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:3][NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][NH:13][CH2:14][C@H:15]([OH:26])[C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([NH:23][CH:24]=[O:25])[CH:17]=2)=[CH:7][CH:6]=1.[ClH:33].O>C(O)(C)C>[ClH:33].[OH:1][C@H:2]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[CH2:3][NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][NH:13][CH2:14][C@H:15]([OH:26])[C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([NH:23][CH:24]=[O:25])[CH:17]=2)=[CH:7][CH:6]=1.[OH:1][C@H:2]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[CH2:3][NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][NH:13][CH2:14][C@H:15]([OH:26])[C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([NH:23][CH:24]=[O:25])[CH:17]=2)=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 9892481Milveterol

Product 2

HCID 9892481MilveterolYield 139.5%HCID 11225217Milveterol hydrochloride

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
40 °C

Procedure

In a 500 mL round bottom flask, compound 1 (5.2 g, 11.9 mmol) was dissolved in 187.9 mL isopropyl alcohol with stirring at 40° C. Complete dissolution was achieved within 10 minutes. The flask was then charged with a solution containing 1.0 N HCl (11.3 mL, 11.3 mmol, 0.95 eq.) and H2O (29.6 mL). The solution was stirred and the product crystallized over several hours. After 6 h, the crystals were isolated by filtration and washed with 15 mL ice-cold 15% water in isopropyl alcohol solution followed by 15 mL of isopropyl alcohol. The crystals were dried under house vacuum for 12-16 h to afford the monohydrochloride salt of compound 1 (3.92 g, 8.3 mmol, 70% yield, 98.89% purity by HPLC) as a white crystalline solid. Water content 0.2%, 1H NMR (300 MHz, DMSO-d6): δ (ppm) 10.13 (s, 1H), 9.62 (m, 1H), 8.93 (br s, 1H), 8.66 (br s, 1H), 8.27 (d, 1H, J=1.92), 8.13 (d, 1H, J=1.65), 7.21-7.40 (m, 5H), 6.86-6.94 (m, 4H), 6.57 (d, 2H, J=8.52), 6.05 (d, 1H, J=3.57), 5.45-5.55 (m, 2H), 4.80 (m, 1H), 4.70 (m, 1H), 2.70-3.24 (m, 8H). Elemental analysis (wt %) calcd for C25H29N3O4.HCl: C, 63.62; H, 6.41; N, 8.90; Cl, 7.51. found: C, 63.47; H, 6.54; N, 8.81; Cl, 7.78.

Workup

  1. dissolutionComplete dissolution
  2. additionThe flask was then charged with a solution
  3. stirringThe solution was stirred
  4. customthe product crystallized over several hours
  5. waitAfter 6 h
  6. customthe crystals were isolated by filtration
  7. washwashed with 15 mL ice-cold 15% water in isopropyl alcohol solution
  8. customThe crystals were dried under house vacuum for 12-16 h

Sources & evidence

ORD record
ord-5516f66664d7493b896bb493eddc91df
Source dataset
uspto-grants-2009_07
Patent number
US07557247B2

Reaction notes

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