Acetic Acid → 1'-(4-chlorophenyl)-6'-methoxy-5',7',8'-trimethyl-2',4'-dihydro-1'H-spiro[cyclobutane-1,3'-quinoline]

HRID 2103067Notes

Reaction equation

HRID 2103067 reaction equation
C(O)(=O)C.FC(F)(F)C(O)=O.[BH4-].[Na+].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[C:30]3[C:25](=[C:26]([CH3:35])[C:27]([O:33][CH3:34])=[C:28]([CH3:32])[C:29]=3[CH3:31])[CH:24](O)[C:23]3([CH2:39][CH2:38][CH2:37]3)[CH2:22]2)=[CH:17][CH:16]=1>C1COCC1.CCOC(C)=O.CCCCCC.O.C(OC(=O)C)C>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[C:30]3[C:25](=[C:26]([CH3:35])[C:27]([O:33][CH3:34])=[C:28]([CH3:32])[C:29]=3[CH3:31])[CH2:24][C:23]3([CH2:39][CH2:38][CH2:37]3)[CH2:22]2)=[CH:17][CH:16]=1

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 4311764Sodium borohydrideHCID 690544051'-(4-chlorophenyl)-6'-methoxy-5',7',8'-trimethyl-2',4'-dihydro-1'H-spiro[cyclobutane-1,3'-quinolin]-4'-ol

Product 1

HCID 690532931'-(4-chlorophenyl)-6'-methoxy-5',7',8'-trimethyl-2',4'-dihydro-1'H-spiro[cyclobutane-1,3'-quinoline]Yield 55.6%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a 2 mL mixture of acetic acid and trifluoroacetic acid (1:1, v/v) cooled in ice bath, was added NaBH4 (71 mg) in portions, followed with 1′-(4-chlorophenyl)-6′-methoxy-5′,7′,8′-trimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinolin]-4′-ol (65 mg) in THF (0.5 mL). After 20 min, the mixture was taken up by ethylacetate and water. After separation of the two phases, the aqueous phase was extracted with more ethylacetate, and the combined organic phases were washed with brine, dried and evaporated to yield a thick oil, which was passed through a silica column (EtOAc/Hexane: 0-5% in 30 min) to give 1′-(4-chlorophenyl)-6′-methoxy-5′,7′,8′-trimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline] (34.6 mg). 1H-NMR (300 MHz, CDCl3) δ=7.2-6.933 (d, 2H); 6.783-6.428 (d, 2H); 3.68 (s, 3H); 3.64 (s, 2H); 2.72 (s, 2H); 2.21 (s, 3H); 2.16 (s, 3H); 1.75 (s, 3H); 1.988-1.542 (m, 6H) ppm. 13C-NMR (75 MHz, CDCl3) δ=152.86, 150.26, 136.97, 129.12, 128.7, 128.11, 128.03, 126.65, 123.67, 119.89, 60.78, 60.39, 40.19, 38.65, 32.78, 15.92, 15.51, 13.02, 12.02 ppm.

Workup

  1. customAfter separation of the two phases
  2. extractionthe aqueous phase was extracted with more ethylacetate
  3. washthe combined organic phases were washed with brine
  4. customdried
  5. customevaporated
  6. customto yield a thick oil, which

Sources & evidence

ORD record
ord-6e220fed051d418fa6f3b2afc053a782
Source dataset
uspto-grants-2009_08
Patent number
US07576094B2

Reaction notes

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