1-Propanol → HCID 68183039, compound

HRID 1615564Notes

Reaction equation

HRID 1615564 reaction equation
C([N:4]1[CH2:9][CH:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=2)[C:7]2[CH:18]=[C:19]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[S:20][C:6]=2[C:5]1=[O:27])C=C.C(O)CC>[Rh](Cl)(Cl)Cl>[Cl:17][C:12]1[CH:11]=[C:10]([CH:8]2[CH2:9][NH:4][C:5](=[O:27])[C:6]3[S:20][C:19]([N:21]4[CH2:22][CH2:23][O:24][CH2:25][CH2:26]4)=[CH:18][C:7]2=3)[CH:15]=[CH:14][C:13]=1[Cl:16]

Participants

4

Reactant 2

HCID 10311-PropanolHCID 68182979HCID 68182979, compound

Product 1

HCID 68183039HCID 68183039, compound

Reagents, catalysts & solvents 1

HCID 24872Rhodium chlorideCatalyst2×

Conditions

Temperature
120 °C

Procedure

A solution of 6-allyl-4-(3,4-dichlorophenyl)-2-(morpholin-4-yl)-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (0.26 g, 0.60 mmol) in 1-propanol (10.0 mL, 134 mmol) was degassed for 10 minutes. Rhodium(III)chloride, (87.0 mg g, 0.41 mmol) was added and the reaction mixture was heated to 120° C. After 18 hours, rhodium(III)chloride (59.6 mg g) was added and the mixture was stirred for additional 18 hours. The reaction was cooled to ambient temperature and quenched by the addition of a solution of saturated aqueous solution of sodium bicarbonate (10.0 mL) and extracted with EtOAc (20.0 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (12 g cartridge, gradient hexanes to 100% EtOAc) to afford the pure product (114 mg g, 49%) as a white solid. The purified racemic mixture was separated into enantiomers on a Chiralpak IA 4.6×250 column using 70/15/15/01% Hexane/IPA/EtOH/DEA, 1.0 mL/minute for 40 minutes. Peak one (13.8 mg, 43.7%) was collected with retention time of 14.9 min. and peak two (14.8 mg, 46.9%) was collected with retention time of 21.5 min., both as a white solid. Absolute configuration of the obtained enantiomers is unknown. LCMS (AA): ES+ 383, 385, 387. 1H NMR (DMSO-d6, 400 MHz): δ 7.59 (d, J=8.4 Hz, 1H), 7.48 (d, J=2.4 Hz, 1H), 7.35 (br s, 1H), 5.88 (s, 1H), 4.19 (t, J=5.6 Hz, 1H), 3.69-3.63 (m, 5H), 3.37 (ddd, J=12.4, 6.0, 3.2 Hz, 1H), 3.13-3.11 (m, 4H).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customquenched by the addition of a solution of saturated aqueous solution of sodium bicarbonate (10.0 mL)
  3. extractionextracted with EtOAc (20.0 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by silica gel column chromatography (12 g cartridge, gradient hexanes to 100% EtOAc)
  8. customto afford the pure product (114 mg g, 49%) as a white solid
  9. customThe purified racemic mixture was separated into enantiomers on a Chiralpak IA 4.6×250 column
  10. customfor 40 minutes
  11. customPeak one (13.8 mg, 43.7%) was collected with retention time of 14.9 min. and peak two (14.8 mg, 46.9%)
  12. customwas collected with retention time of 21.5 min.

Sources & evidence

ORD record
ord-c72945a5d83c4d2dba2cd1c327e3cc21
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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