2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(((S)-3-hydroxypyrrolidin-1-yl)sulfonyl)benzamide

HRID 1849562Notes

Reaction equation

HRID 1849562 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:39]([Cl:40])=[CH:38][C:16]([C:17]([NH:19][S:20]([N:23]4[CH2:27][CH2:26][C@H:25]([O:28]CC5C=CC(OC)=CC=5)[CH2:24]4)(=[O:22])=[O:21])=[O:18])=[C:15]([F:41])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>ClCCl.O>[C:1]12([CH2:11][O:12][C:13]3[C:39]([Cl:40])=[CH:38][C:16]([C:17]([NH:19][S:20]([N:23]4[CH2:27][CH2:26][C@H:25]([OH:28])[CH2:24]4)(=[O:22])=[O:21])=[O:18])=[C:15]([F:41])[CH:14]=3)[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2

Participants

5

Reactant 2

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 867029064-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(((S)-3-((4-methoxybenzyl)oxy)pyrrolidin-1-yl)sulfonyl)benzamide

Product 1

HCID 867029074-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(((S)-3-hydroxypyrrolidin-1-yl)sulfonyl)benzamideYield 58.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(((S)-3-((4-methoxybenzyl)oxy)pyrrolidin-1-yl)sulfonyl)benzamide (0.17 g, 0.28 mmol) in dichloromethane (18 mL) and water (2 mL) was added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.08 g, 0.36 mmol) at ambient temperature and stirred for 16 h. Water (20 mL) was added and the mixture extracted with ethyl acetate (80 mL×2), the combined organics were washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was filtered through a short silicon gel column, eluted with 5%-60% gradient ethyl acetate in hexanes to give the title compound as colorless solid (0.08 g, 55%): 1H NMR (300 MHz, DMSO-d6) δ 11.73 (s, 1H), 7.70 (d, J=7.5 Hz, 1H), 7.21 (d, J=12.4 Hz, 1H), 5.07 (brs, 1H), 4.32-4.27 (m, 1H), 3.71 (s, 2H), 3.56-3.48 (m, 3H), 3.23-3.19 (m, 1H), 1.99 (s, 3H), 1.93-1.63 (m, 14H); MS (ES+) m/z 487.2, 489.1 (M+1); MS (ES−) m/z 485.3, 487.3 (M−1).

Workup

  1. extractionthe mixture extracted with ethyl acetate (80 mL×2)
  2. washthe combined organics were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. filtrationThe residue was filtered through a short silicon gel column
  6. washeluted with 5%-60% gradient ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e2e0fa909f6546f4b4270f8cef307bb7
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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