Dicyclohexylcarbodiimide → (R)-((R)-quinuclidin-3-yl) 2-(tert-butoxycarbonylamino)-2-phenylacetate

HRID 1529524Notes

Reaction equation

HRID 1529524 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:19]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[C@@H:21](O)[CH2:20]2.C1(N=C=NC2CCCCC2)CCCCC1.O.ON1C2C=CC=CC=2N=N1>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([O:12][C@@H:21]1[CH:22]2[CH2:25][CH2:26][N:19]([CH2:24][CH2:23]2)[CH2:20]1)=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 914043-Quinuclidinol, (-)-HCID 2755953(2R)-2-{[(tert-butoxy)carbonyl]amino}-2-phenylacetic acidHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 67607970(R)-((R)-quinuclidin-3-yl) 2-(tert-butoxycarbonylamino)-2-phenylacetateYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(R)-2-((tert-Butoxycarbonyl)amino)-2-phenylacetic acid (5.0 g, 19.9 mmol), (R)-quinuclidin-3-ol (3.8 g, 29.8 mmol), N,N′-Dicyclohexylcarbodiimide (4.72 g, 22.9 mmol) and 1-hydroxybenzotriazole hydrate (3.09 g, 22.9 mmol) where mixed together in tetrahydrofuran (175 mL) and stirred at ambient temperature for 18 hours. After this time the reaction mixture was filtered through a pad of Celite® and concentrated in vacuo. The resulting crude was partitioned between ethyl acetate (100 mL) and 10% aqueous sodium carbonate solution (50 mL), the resulting organic fractions were dried over magnesium sulfate, filtered and the solvent was removed in vacuo. Trituration with cold methanol gave the title compound as a white solid (898 mg, 17%) as a single diastereoisomer.

Workup

  1. filtrationAfter this time the reaction mixture was filtered through a pad of Celite®
  2. concentrationconcentrated in vacuo
  3. customThe resulting crude was partitioned between ethyl acetate (100 mL) and 10% aqueous sodium carbonate solution (50 mL)
  4. dry with materialthe resulting organic fractions were dried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-4f20aec3b48a41eb953fe5f2617ab8ca
Source dataset
uspto-grants-2015_07
Patent number
US09090606B2

Reaction notes

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