Ethylene Glycol → HCID 178515371, compound

HRID 718862Notes

Reaction equation

HRID 718862 reaction equation
[OH:1][C:2]1[N:7]=[CH:6][C:5]2[C:8]3([CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH:9]3[CH2:10][CH2:11][CH2:12][C:4]=2[CH:3]=1.[CH2:25](O)[CH2:26][OH:27].CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[N:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[CH2:18][C:8]12[CH2:16][CH2:15][C:14]3([O:27][CH2:26][CH2:25][O:17]3)[CH2:13][CH:9]1[CH2:10][CH2:11][CH2:12][C:4]1[CH:3]=[C:2]([OH:1])[N:7]=[CH:6][C:5]=12

Participants

5

Reactant 3

HCID 174Ethylene GlycolHCID 6101p-Toluenesulfonic acidHCID 178515480HCID 178515480, compound

Product 1

HCID 178515371HCID 178515371, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A flask fitted with a Dean-Stark apparatus was charged with rac-(7aR,11aS)-3-hydroxy-11a-(pyridin-2-ylmethyl)-6,7,7a,8,11,11a-hexahydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridin-9(10H)-one (132, R2=Pyridin-2-ylmethyl) (6.8 g, 21.09 mmol), toluene (250 mL), ethane-1,2-diol (4.76 mL, 85 mmol) and pTSA (0.401 g, 2.109 mmol). The mixture was heated to reflux for about 2 h, cooled to rt then concentrated on under reduced pressure. The material was treated with sat. aq. NaHCO3 (50 mL), water (50 mL) and EtOAc (˜100 mL). The mixture was stirred for about 10 min then the solids were collected by filtration and washed with EtOAc (˜15 mL). The material was dried under vacuum. The filtrate layers were separated then the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic solutions were dried over MgSO4, filtered then combined with solids from the first filtration and concentrated under reduced pressure to yield rac-(7aR,11aS)-11a-(pyridin-2-ylmethyl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolan]-3-ol (143, R2=Pyridin-2-ylmethyl) (7.25 g, 94%); LC/MS, method 3, Rt=1.49 min, MS m/z 367 (M+H)+. 1H NMR (400 MHz, DMSO) δ 10.95 (s, 1H), 8.37-8.36 (m, 1H), 7.51-7.46 (m, 1H), 7.10-7.07 (m, 1H), 6.54 (s, 1H), 6.51 (d, J=7.8 Hz, 1H), 6.14 (s, 1H), 3.92-3.81 (m, 4H), 3.33 (d, J=13.3 Hz, 1H), 3.20-3.13 (m, 1H), 3.04 (d, J=13.3 Hz, 1H), 2.69-2.64 (m, 1H), 2.14-2.06 (m, 1H), 2.04-1.96 (m, 1H), 1.91-1.77 (m, 1H), 1.75-1.47 (m, 7H), 1.41-1.23 (m, 1H).

Workup

  1. customA flask fitted with a Dean-Stark apparatus
  2. temperatureThe mixture was heated
  3. temperatureto reflux for about 2 h
  4. concentrationthen concentrated on under reduced pressure
  5. additionThe material was treated with sat. aq. NaHCO3 (50 mL), water (50 mL) and EtOAc (˜100 mL)
  6. filtrationthe solids were collected by filtration
  7. washwashed with EtOAc (˜15 mL)
  8. customThe material was dried under vacuum
  9. customThe filtrate layers were separated
  10. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  11. dry with materialThe combined organic solutions were dried over MgSO4
  12. filtrationfiltered
  13. filtrationthen combined with solids from the first filtration
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0c7bfac2d12f4009a1d60b246498a746
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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