Triethylamine → (S)-3-(1-carbamoyl-1,1-diphenylmethyl)-1-(7-hydroxyhept-1-yl)pyrrolidine

HRID 1181507Notes

Reaction equation

HRID 1181507 reaction equation
[C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][NH:19][CH2:18]1)([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2].C(N(CC)CC)C.Br[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][OH:37]>C(#N)C>[C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][OH:37])[CH2:18]1)([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 662841-Heptanol, 7-bromo-HCID 13633758(S)-2,2-Diphenyl-2-(pyrrolidin-3-yl)acetamide

Product 1

HCID 67428481(S)-3-(1-carbamoyl-1,1-diphenylmethyl)-1-(7-hydroxyhept-1-yl)pyrrolidineYield 56%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
50 °C

Procedure

To a stirred solution of (S)-3-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (40 g, 142.7 mmol) and triethylamine (59.6 mL, 428 mmol) in acetonitrile (1.1 L) at 40° C. under a nitrogen atmosphere was added 7-bromo-1-heptanol (24 mL, 146 mmol) in acetonitrile (100 mL) dropwise. The reaction mixture was heated to 50° C. for 9 hours. The reaction mixture was allowed to cool before removing the solvent under reduced pressure. The crude residue was dissolved in dichloromethane (500 mL) and the organic layer washed with saturated aqueous sodium bicarbonate (2×300 mL), followed by water (300 mL) and saturated aqueous sodium chloride (300 mL), and then dried over magnesium sulfate (10 g). The magnesium sulfate was filtered off and washed with dichloromethane (100 mL). The solvent was then removed in vacuo to give the crude product which was purified on a short column (SiO2) by varying the eluant from 19:1:0.1 to 3:1:0.1 CH2Cl2/MeOH/NH4OH to give 31.35 g of the title intermediate as a white solid (56% yield; >95% purity by HPLC Method A).

Workup

  1. temperatureto cool
  2. custombefore removing the solvent under reduced pressure
  3. dissolutionThe crude residue was dissolved in dichloromethane (500 mL)
  4. washthe organic layer washed with saturated aqueous sodium bicarbonate (2×300 mL)
  5. dry with materialdried over magnesium sulfate (10 g)
  6. filtrationThe magnesium sulfate was filtered off
  7. washwashed with dichloromethane (100 mL)
  8. customThe solvent was then removed in vacuo
  9. customto give the crude product which
  10. customwas purified on a short column (SiO2)

Sources & evidence

ORD record
ord-7a35e88ed6154fa29938258a3e41ddc8
Source dataset
uspto-grants-2007_10
Patent number
US07285564B2

Reaction notes

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