Dimethylformamide → 7-{[1-(4-Chlorophenyl)cyclopropyl]carbonyl}-4,4-dimethyl-1-oxa-7-azaspiro[4,4]nonane

HRID 504437Notes

Reaction equation

HRID 504437 reaction equation
[CH3:1][CH:2]1[C:5]([CH3:7])([CH3:6])[C:4]2([CH2:11][CH2:10][N:9]([C:12]([O:14]C(C)(C)C)=O)[CH2:8]2)[O:3]1.CC1(C)C2(CCN(C(OC(C)(C)C)=O)C2)OCC1.C(O)(C(F)(F)F)=O.CN(C)C=O.[Cl:49][C:50]1[CH:55]=[CH:54][C:53]([C:56]2(C(O)=O)[CH2:58][CH2:57]2)=[CH:52][CH:51]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>>[Cl:49][C:50]1[CH:55]=[CH:54][C:53]([C:56]2([C:12]([N:9]3[CH2:10][CH2:11][C:4]4([O:3][CH2:1][CH2:2][C:5]4([CH3:6])[CH3:7])[CH2:8]3)=[O:14])[CH2:58][CH2:57]2)=[CH:52][CH:51]=1

Participants

8

Reactant 7

HCID 6228DimethylformamideHCID 6422Trifluoroacetic acid2×HCID 81531DiisopropylethylamineHCID 986061-(p-Chlorophenyl)cyclopropanecarboxylic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 666619971-Oxa-7-azaspiro[4.4]nonane-7-carboxylic acid, 4,4-dimethyl-, 1,1-dimethylethyl esterHCID 66662740Tert-butyl 2,3,3-trimethyl-1-oxa-6-azaspiro[3.4]octane-6-carboxylate

Product 1

HCID 666621557-{[1-(4-Chlorophenyl)cyclopropyl]carbonyl}-4,4-dimethyl-1-oxa-7-azaspiro[4,4]nonane

Procedure

A mixture of tert-butyl 2,3,3-trimethyl-1-oxa-6-azaspiro[3.4]octane-6-carboxylate (25.0 mg, 0.0000979 mol) and tert-butyl 4,4-dimethyl-1-oxa-7-azaspiro[4.4]nonane-7-carboxylate (25.0 mg, 0.0000979 mol) was treated with 1 mL of TFA at rt for 30 min. The volatiles were removed in-vacuo and the resultant TFA salt was used directly in next step. To a mixture of the above made TFA salt in N,N-dimethylformamide (0.50 mL, 0.0064 mol) were added 1-(4-chlorophenyl)cyclopropanecarboxylic acid (38.5 mg, 0.000196 mol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (104 mg, 0.000235 mol), followed by N,N-diisopropylethylamine (0.0853 mL, 0.000490 mol). The mixture was stirred at rt for 2 h and then the product was isolated and purified by RP-HPLC. LCMS (M+H) 334.2.

Workup

  1. customThe volatiles were removed in-vacuo
  2. additionTo a mixture of the
  3. customthe product was isolated
  4. custompurified by RP-HPLC

Sources & evidence

ORD record
ord-6591c01d78264802a23f06d9e2f3c555
Source dataset
uspto-grants-2010_08
Patent number
US07776874B2

Reaction notes

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