Triethylamine → (1S,5R)-3-(3-{[(1,1-Dimethylethyl)(Dimethyl)Silyl]Oxy}Propyl)-1-[2-Fluoro-4-(Trifluoromethyl)Phenyl]-3-Azabicyclo[3.1.0]Hexane

HRID 254444

Reaction equation

HRID 254444 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C@:12]12[CH2:17][C@H:16]1[CH2:15][NH:14][CH2:13]2.Br[CH2:19][CH2:20][CH2:21][O:22][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24].C(N(CC)CC)C.N[C@H](C(O)=O)CC1C=C2C(C=CC=C2)=CC=1>C1COCC1>[CH3:28][C:26]([Si:23]([CH3:25])([CH3:24])[O:22][CH2:21][CH2:20][CH2:19][N:14]1[CH2:15][C@H:16]2[C@:12]([C:3]3[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]=3[F:1])([CH2:17]2)[CH2:13]1)([CH3:27])[CH3:29]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 1859152-NaphthylalanineHCID 607486(3-Bromopropoxy)(tert-butyl)dimethylsilaneHCID 59346768(1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 59759997(1S,5R)-3-(3-{[(1,1-Dimethylethyl)(Dimethyl)Silyl]Oxy}Propyl)-1-[2-Fluoro-4-(Trifluoromethyl)Phenyl]-3-Azabicyclo[3.1.0]HexaneYield 97.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (150 mg, 0.6 mmol), [(3-bromopropyl)oxy](1,1-dimethylethyl)dimethylsilane (233 mg, 0.92 mmol), triethylamine (185 mg, 1.83 mmol) and Nal (20 mg) in THF (2 mL) was stirred at r.t. for 20 h. The reaction mixture was concentrated under vacuum, water was added and the aqueous phase was extracted with EtOAc. The organic phase was dried over Na2SO4 and filtered. The filtrate was concentrated under vacuum and the crude was purified by column chromatography (eluting with EtOAc/cyclohexane 3/7) to give 245 mg of the title compound.

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum, water
  2. additionwas added
  3. extractionthe aqueous phase was extracted with EtOAc
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under vacuum
  7. customthe crude was purified by column chromatography (eluting with EtOAc/cyclohexane 3/7)

Sources & evidence

ORD record
ord-d661de3d79454f38b7d20a768ef01a40
Source dataset
uspto-grants-2011_01
Patent number
US07875643B2

Linked notes

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