Methanol → HCID 59264949, compound

HRID 2355792Notes

Reaction equation

HRID 2355792 reaction equation
C([O:4][C@@H:5]1[CH2:9][C:8](=O)[N:7]([C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@H:12]2[O:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:22]([O:34][CH3:35])[CH:21]=2)[C:6]1=O)(=O)C.B.C1COCC1.CO>C1COCC1>[CH2:27]([O:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][CH2:18][O:17][C@@H:12]2[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]2[N:7]2[CH2:8][CH2:9][C@@H:5]([OH:4])[CH2:6]2)=[CH:21][C:22]=1[O:34][CH3:35])[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 2723981Borane;tetrahydrofuranHCID 58856249HCID 58856249, compound

Product 1

HCID 59264949HCID 59264949, compoundYield 119.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (1R,2R)-1-{2-[2-(4-benzyloxy-3-methoxyphenyl)ethoxy]-cyclohexyl}-(3R)-2,5-dioxopyrrolidin-3-yl acetate (49.0 g, 100 mmol) in anhydrous THF (100 mL) under nitrogen was added slowly BH3.THF (1.0 M solution in THF, 400 mmol, 400 mL). The solution was heated to 80° C. and stirred for 3 hours. The solution was cooled to ambient temperature and methanol (100 mL) was added slowly until no more bubbling was observed. The solution was concentrated and methanolic HCl (1.25 M solution in CH3OH, 500 mL) was added. The solution was heated to 80° C. and stirred for 1 hour. The cooled solution was then concentrated to afford (1R,2R)-1-{2-[2-(4-benzyloxy-3-methoxyphenyl)ethoxy]cyclohexyl}-(3R)-pyrrolidin-3-ol (50.8 g, quantitative yield) as a yellow syrup. The crude product was used in the next step without further purification; 1H NMR (400 MHz, CDCl3) δ 11.45 (br, s, 1H), 7.50-7.10 (m, 5H), 6.90-6.60 (m, 3H), 4.22 (br, s, 1H), 4.00-3.85 (m, 5H), 3.75-3.55 (m, 2H), 3.35-2.50 (m, 7H), 2.45-2.20 (m, 2H), 2.08 (br, s, 1H), 1.90-1.50 (m, 3H), 1.35-1.05 (m, 6H); MS (ESI): 426.2 [M+H]+

Workup

  1. temperatureThe solution was cooled to ambient temperature
  2. customno more bubbling
  3. concentrationThe solution was concentrated
  4. additionmethanolic HCl (1.25 M solution in CH3OH, 500 mL) was added
  5. temperatureThe solution was heated to 80° C.
  6. stirringstirred for 1 hour
  7. concentrationThe cooled solution was then concentrated

Sources & evidence

ORD record
ord-df48eeeda7d64d80bf4dff80fadea504
Source dataset
uspto-grants-2010_07
Patent number
US07754897B2

Reaction notes

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