Hydrochloric Acid → 5-Chloro-2-(2-chloro-4-iodo-phenylamino)-N-((S)-2,3-dihydroxy-propoxy)-3,4-difluoro-benzamide

HRID 2218478Notes

Reaction equation

HRID 2218478 reaction equation
[Cl:1][C:2]1[C:3]([F:30])=[C:4]([F:29])[C:5]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=2[Cl:28])=[C:6]([CH:19]=1)[C:7]([NH:9][O:10][CH2:11][C@@H:12]1[CH2:16][O:15]C(C)(C)[O:13]1)=[O:8].Cl>O1CCCC1>[Cl:1][C:2]1[C:3]([F:30])=[C:4]([F:29])[C:5]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=2[Cl:28])=[C:6]([CH:19]=1)[C:7]([NH:9][O:10][CH2:11][C@@H:12]([OH:13])[CH2:16][OH:15])=[O:8]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 865914595-chloro-2-(2-chloro-4-iodo-phenylamino)-N-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-benzamide

Product 1

HCID 101286785-Chloro-2-(2-chloro-4-iodo-phenylamino)-N-((S)-2,3-dihydroxy-propoxy)-3,4-difluoro-benzamideYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 3 L single necked round bottomed flask equipped with a magnetic stirrer was charged with a solution of 5-chloro-2-(2-chloro-4-iodo-phenylamino)-N-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-benzamide (69.9 g, 122 mmol) in tetrahydrofuran (1.5 L). Aqueous 1N hydrochloric acid (500 mL) solution was added and the reaction mixture was stirred at ambient temperature for 18 hrs. The reaction mixture was concentrated and extracted with ethyl acetate (3×800 mL). The organic extracts were washed with saturated aqueous sodium bicarbonate (500 ml) and brine (500 ml), and dried (MgSO4). The crude pale yellow solid was recrystallized from ethyl acetate/hexane and dried at 70° C. in vacuum oven to afford 5-Chloro-2-(2-chloro-4-iodo-phenylamino)-N-((S)-2,3-dihydroxy-propoxy)-3,4-difluoro-benzamide (35 g, 54%) as pale yellow crystals: m.p. 153-154° C.; [α]=+3.36° (c=1.04, methanol); 1H NMR (d6-DMSO) δ 12.02 (s, 1H), 8.85 (s, 1H), 7.74 (s, 1H), 7.64 (d, 1H), 7.45 (d, 1H), 6.66 (t, 1H), 4.82 (s, 1H), 4.58 (s, 1H), 3.88 (m, 2H), 3.74 (m, 3H); 19F NMR (d6-DMSO) δ −133.21 (s, 1F), −137.18 (s, 1F); MS (m/z): 534 (68), 532 (100), 483 (28), 481 (41), 440 (51). Anal. calcd/found for C16H13Cl2F2IN2O4: C, 36.05/36.36; H, 2.46/2.38; N, 5.25/5.30; F, 7.13/7.15; Cl, 13.30/13.76; I, 23.80/23.83.

Workup

  1. customA 3 L single necked round bottomed flask equipped with a magnetic stirrer
  2. concentrationThe reaction mixture was concentrated
  3. extractionextracted with ethyl acetate (3×800 mL)
  4. washThe organic extracts were washed with saturated aqueous sodium bicarbonate (500 ml) and brine (500 ml)
  5. dry with materialdried (MgSO4)
  6. customThe crude pale yellow solid was recrystallized from ethyl acetate/hexane
  7. customdried at 70° C. in vacuum oven

Sources & evidence

ORD record
ord-67dfd10fbdbd45c3b96472e444bcbe18
Source dataset
uspto-grants-2008_08
Patent number
US07411001B2

Reaction notes

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