Dimethyl Sulfoxide → HCID 57911403, compound

HRID 1666140Notes

Reaction equation

HRID 1666140 reaction equation
CS(C)=O.[F:5][C:6]1[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:7]=1[C@@H:13]1[CH2:23][CH2:22][C@@H:21]([OH:24])[C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:15]2[CH2:14]1.CCN(CC)CC.O>C(Cl)Cl.CCOC(C)=O>[F:5][C:6]1[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:7]=1[CH:13]1[CH2:23][CH2:22][C:21](=[O:24])[C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:15]2[CH2:14]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 8471TriethylamineHCID 57911431HCID 57911431, compound

Product 1

HCID 57911403HCID 57911403, compoundYield 72.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In an oven-dried 100 mL round-bottomed flask was OXALYL CHLORIDE (0.131 mL, 1.497 mmol) in CH2Cl2 (4 mL) to give a colorless solution at −55° C. under nitrogen. DMSO (0.212 mL, 2.99 mmol) was added dropwise over 10 min. After the solution was stirred for an additional 30 min, (6R,9R)-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ol (206 mg, 0.748 mmol) (racemic, azeotroped with dry benzene) dissolved in 2 ml CH2Cl2 (plus 2 ml rinse) was added via canuula over 5 min. The reaction mixture was stirred at −50-−55° C. for an additional 40 min (the solution became milky). Et3N (0.521 mL, 3.74 mmol) was added via syringe at −50° C. and the reaction mixture was stirred for 30 min. Water and EtOAc were added, and the layers were separated. The aqueous layer was extracted with EtOAc. The combined organic layers were dried with Na2SO4, and concentrated to a tan oil. TLC (1/1 EtOAc/hexane) showed two spots: the major more polar (comparable to cis-alcohol) and a little SM. Purification by FCC up to 60% EtOAc/hexane afforded the desired product as a colorless oil (148 mg, 72%), plus a little recovered sm. MS(ESI)[M+H+]=274.30.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.57 (dd, J=4.66, 1.64 Hz, 1 H) 7.39 (d, J=7.81 Hz, 1 H) 7.20-7.31 (m, 1 H) 6.83-7.04 (m, 2 H) 6.72 (t, J=6.92 Hz, 1 H) 3.50 (dd, J=9.32, 6.30 Hz, 1 H) 3.09 (d, J=6.30 Hz, 2 H) 2.84-2.99 (m, 1 H) 2.68-2.84 (m, 1 H) 2.03-2.17 (m, 1 H) 1.85-2.02 (m, 1 H); 13C NMR (100 MHz, CHLOROFORM-d) δ ppm 203.43, 154.56, 152.00-149.39 (dd, J=13.4 and 247 Hz), 149.52-146.94 (dd, J=12.5 and 247 Hz), 148.83, 138.77, 134.44, 134.22 (d, J=11.0 Hz), 125.87, 124.16, 122.36, 115.40 (d, J=17.0 Hz), 39.62, 36.83, 35.19, 27.33.

Workup

  1. wash(plus 2 ml rinse)
  2. additionwas added via canuula over 5 min
  3. stirringThe reaction mixture was stirred at −50-−55° C. for an additional 40 min (the solution
  4. stirringthe reaction mixture was stirred for 30 min
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc
  7. dry with materialThe combined organic layers were dried with Na2SO4
  8. concentrationconcentrated to a tan oil
  9. customPurification by FCC up to 60% EtOAc/hexane

Sources & evidence

ORD record
ord-38c9a5b1bb694f24902dad0c28a4df1a
Source dataset
uspto-grants-2011_10
Patent number
US08044043B2

Reaction notes

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