Diisopropylethylamine → (1R)-1'-({1-[4-(Pyridin-4-ylmethoxy)phenyl]cyclopropyl}-carbonyl)-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

HRID 557831Notes

Reaction equation

HRID 557831 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH:14]1[CH2:18][CH2:17][C@@:16]2([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[C:20](=[O:27])[O:19]2)[CH2:15]1.[CH3:28][C:29]1(C)[C@@H]2CC[C@@:30]1([CH2:37]S(O)(=O)=O)[C:31](=O)[CH2:32]2.F[P-](F)(F)(F)(F)F.[N:50]1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[N:50]1[CH:32]=[CH:31][C:30]([CH2:37][O:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3([C:11]([N:14]4[CH2:18][CH2:17][C@@:16]5([C:22]6[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=6[C:20](=[O:27])[O:19]5)[CH2:15]4)=[O:13])[CH2:9][CH2:10]3)=[CH:6][CH:7]=2)=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 225049291-(4-Hydroxyphenyl)cyclopropane-1-carboxylic acidHCID 86602274[(1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl]methanesulfonic acid (1R)-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

Product 1

HCID 66661855(1R)-1'-({1-[4-(Pyridin-4-ylmethoxy)phenyl]cyclopropyl}-carbonyl)-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-oneYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-(4-hydroxyphenyl)cyclopropanecarboxylic acid (0.20 g, 1.1 mmol), [(1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl]methanesulfonic acid-(1R)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one salt (0.47 g, 1.1 mmol), Benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.55 g, 1.2 mmol), and N,N-diisopropylethylamine (0.49 ml, 2.8 mmol) in methylene chloride (3 ml) was stirred at r.t. overnight. Then the reaction was quenched with water, and the reaction mixture was extracted with ethyl acetate. The extract was washed with 1N HCl aqueous solution (x2), water and brine successively; then dried over Na2SO4; and then filtered. The filtrate was concentrated to afford the desired product (0.35 g, yield: 89%).

Workup

  1. customThen the reaction was quenched with water
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washThe extract was washed with 1N HCl aqueous solution (x2), water and brine successively
  4. dry with materialthen dried over Na2SO4
  5. filtrationand then filtered
  6. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-1e7d133630fa422d98624dfb404f66cf
Source dataset
uspto-grants-2011_11
Patent number
US08058288B2

Reaction notes

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