Water → Milveterol

HRID 226286Notes

Reaction equation

HRID 226286 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.[Cl:33]Cl.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 962WaterHCID 24526ChlorineHCID 9892481Milveterol2×

Product 2

HCID 9892481MilveterolYield 67%HCID 11225217Milveterol hydrochloride

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent3×

Conditions

Temperature
57.5 °C

Procedure

A 250 mL three-necked flask was charged with a hydrochloride salt of compound 1 having 1.52 equivalents of chlorine per mole of compound 1 (6.1 g, 12 mmol) and 1:1 isopropanol:water (98 mL). The mixture was heated to 50-65° C. to dissolve the solid and the solution was stirred at 50-60° C. Isopropanol (98 mL) was slowly added over 30 min at 50-60° C. and the solution was cooled to room temperature over 3 h. Isopropanol (98 mL) was slowly added over 30 min and the solution was stirred at room temperature for 7 h. The crystals were isolated by filtration, washed with isopropanol (30 mL) and dried under vacuum for 16 h to yield the monohydrochloride salt of compound 1 (3.8 g, 8.0 mmol, 67% yield, 99.7% purity by HPLC)

Workup

  1. dissolutionto dissolve the solid
  2. temperaturethe solution was cooled to room temperature over 3 h
  3. stirringthe solution was stirred at room temperature for 7 h
  4. customThe crystals were isolated by filtration
  5. washwashed with isopropanol (30 mL)
  6. customdried under vacuum for 16 h

Sources & evidence

ORD record
ord-61bcee2384c2471f86e6e3764162ff60
Source dataset
uspto-grants-2009_07
Patent number
US07557247B2

Reaction notes

Loading…