3,5-Dinitrobenzoyl chloride → (3S)-4-(4-fluorophenoxy)-3-(3',5'-dinitrobenzoyl)oxy-1-butyne

HRID 2307604Notes

Reaction equation

HRID 2307604 reaction equation
[F:1][C:2]1[CH:13]=[CH:12][C:5]([O:6][CH2:7][C@@H:8]([OH:11])[C:9]#[CH:10])=[CH:4][CH:3]=1.[N+:14]([C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([N+:26]([O-:28])=[O:27])[CH:25]=1)[C:20](Cl)=[O:21])([O-:16])=[O:15].C(N(CC)CC)C.CN(C1C=CC=CN=1)C>C(Cl)Cl>[F:1][C:2]1[CH:13]=[CH:12][C:5]([O:6][CH2:7][C@@H:8]([O:11][C:20](=[O:21])[C:19]2[CH:18]=[C:17]([N+:14]([O-:16])=[O:15])[CH:25]=[C:24]([N+:26]([O-:28])=[O:27])[CH:23]=2)[C:9]#[CH:10])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 74323,5-Dinitrobenzoyl chlorideHCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 865887753-Butyn-2-ol, 1-(4-fluorophenoxy)-, (2S)-

Product 1

HCID 20744976(3S)-4-(4-fluorophenoxy)-3-(3',5'-dinitrobenzoyl)oxy-1-butyne

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3S)-4-(4-fluorophenoxy)-3-hydroxy-1-butyne (est. 490 mmol) in methylene chloride (1 L) was added 3,5-dinitrobenzoyl chloride (125 g, 539 mmol) at between −5° C. and 0° C., followed by slow addition of triethylamine (10.8 mL, 77 mmol) and a catalytic amount of dimethylaminopyridine (DMAP) (20 mg). After the mixture was stirred at ambient temperature for 40 minutes, the reaction mixture was cautiously partitioned between methylene chloride and aqueous NaHCO3. The aqueous layer was extracted with dichloromethane, and the combined organic layers were washed with water and brine, and dried over Na2SO4. The solution was filtered through a pad of silica gel with methylene chloride which gave crude product as a tan solid. Rapid recrystallization from 99:1 mixture of methanol:acetic acid (5 L) gave 101 g of the enantiomerically enriched product, (3S)-4-(4-fluorophenoxy)-3-(3′,5′-dinitrobenzoyl)oxy-1-butyne, a compound of formula (BBa) as fluffy white needles. This material was determined to have greater than 98% ee by analytical HPLC using a Diacel Chiralpak AD® (4.6×250 mm, 60% 2-propanol/hexane, 1 mL/min), which separates the (R) (11.5 min) and the (S) (19.3 min) enantiomers; 1H NMR (CDCl3) δ 2.65 (s, 1H), 4.40 (m, 2H), 6.05 (m, 1H), 6.90 (m, 2H), 7.0 (t, 2H), 9.15 (s, 2H), 9.25 (s, 1H) ppm.

Workup

  1. customthe reaction mixture was cautiously partitioned between methylene chloride and aqueous NaHCO3
  2. extractionThe aqueous layer was extracted with dichloromethane
  3. washthe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe solution was filtered through a pad of silica gel with methylene chloride which
  6. customgave crude product as a tan solid
  7. customRapid recrystallization
  8. additionfrom 99:1 mixture of methanol

Sources & evidence

ORD record
ord-9b5fcebc53b745bb9517c87bb5a871af
Source dataset
uspto-grants-2004_12
Patent number
US06831186B2

Reaction notes

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