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

HRID 2279935Notes

Reaction equation

HRID 2279935 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

A mixture of (R)-2-((tert-Butoxycarbonyl)amino)-2-phenylacetic acid (5.0 g, 19.9 mmol), (R) enantiomeric pure form commercially available or obtainable from I-41 with known methods e.g. chiral preparative SFC, (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) in tetrahydrofuran (175 mL) was stirred at room temperature for 18 h. After this time the reaction mixture was filtered through a pad of Celite® and concentrated in vacuo. The residue was partitioned between ethyl acetate (100 mL) and 10% aqueous sodium carbonate solution (50 mL), and the 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 residue was partitioned between ethyl acetate (100 mL) and 10% aqueous sodium carbonate solution (50 mL)
  4. dry with materialthe organic fractions were dried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-aacf24cd20dd4b3aac892368da0ffcc1
Source dataset
uspto-grants-2015_09
Patent number
US09133185B2

Reaction notes

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