Acetic Acid → (s)-3-(1-Carbamoyl-1,1-diphenylmethyl)-1-(hex-5-yn-1-yl)pyrrolidine

HRID 1181509Notes

Reaction equation

HRID 1181509 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(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[CH:40](=O)[CH2:41][CH2:42][CH2:43][C:44]#[CH:45]>ClCCl>[C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:45][CH2:44][CH2:43][CH2:42][C:41]#[CH:40])[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

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 9898802Hex-5-ynalHCID 13633758(S)-2,2-Diphenyl-2-(pyrrolidin-3-yl)acetamide

Product 1

HCID 87396490(s)-3-(1-Carbamoyl-1,1-diphenylmethyl)-1-(hex-5-yn-1-yl)pyrrolidineYield 83%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (S)-3-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (64.4 g, 0.23 mol); sodium triacetoxyborohydride (50.9 g, 0.24 mol) and acetic acid (13 mL, 0.23 mol) in dichloromethane (511 mL) at room temperature, was added a solution of hex-5-yn-1-al (26.14 g, 0.27 mol) in dichloromethane (256 mL). The reaction mixture stirred at room temperature overnight (ca. 8 hours) and then the reaction mixture was quenched by addition of concentrated hydrochloric acid (30 mL) and stirring was continued for 1 hour at room temperature. The mixture was then diluted with water (750 mL) and made basic to pH 5 using 10 N sodium hydroxide (18 mL). The layers were separated and the organic layer was washed with 1 N sodium hydroxide (200 mL). The organic layer was dried over magnesium sulfate (10 g); filtered and then concentrated in vacuo to afford 67.6 g of the title intermediate as a yellow gummy solid (83% yield).

Workup

  1. customthe reaction mixture was quenched by addition of concentrated hydrochloric acid (30 mL)
  2. stirringstirring
  3. waitwas continued for 1 hour at room temperature
  4. additionThe mixture was then diluted with water (750 mL)
  5. customThe layers were separated
  6. washthe organic layer was washed with 1 N sodium hydroxide (200 mL)
  7. dry with materialThe organic layer was dried over magnesium sulfate (10 g)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7ce2f8e8ba30404ab8938d9d6c15945b
Source dataset
uspto-grants-2007_10
Patent number
US07285564B2

Reaction notes

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