Carbamate → HCID 11647413, compound

HRID 349723Notes

Reaction equation

HRID 349723 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[CH2:6][O:7][CH2:8][C:9]([CH3:19])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:10][C:11]#[N:12].[C:29]([O-])([O-])=O.[K+].[K+].ClC(OC)=O.C(=O)([O-])N.[Li].[H-]>C(Cl)Cl.C1COCC1>[F:1][C:2]([F:27])([F:28])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:25])([F:24])[F:26])[CH:22]=1)[CH2:6][O:7][CH2:8][C:9]([CH3:19])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:10][CH2:11][NH:12][CH3:29]

Participants

9

Reactant 6

HCID 276CarbamateHCID 6586Methyl chloroformateHCID 11430Potassium CarbonateHCID 166653HydrideHCID 3028194LithiumHCID 86602763HCID 86602763, compound

Product 1

HCID 11647413HCID 11647413, compoundYield 17.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

4-(3,5-bis(trifluoromethyl)benzyloxy)-3-methyl-3-phenylbutanenitrile (46.2 mg, 0.115 mmol) was treated with neat borane-dimethylsulfide complex for 2 hour at room temperature until completion of reaction. The excess amount of borane was removed under nitrogen stream. The residue was quenched further with methanol and then heated at 80° C. for 1 hour to decompose the borane-amine complex. The resultant solution was concentrated and re-dissolved in CH2Cl2. It was washed with brine and dried with sodium sulfate. After concentration, the residue was mixed with K2CO3 (200 mg) and methyl chloroformate (21.8 mg, 0.23 mmol) in anhydrous CH2Cl2. After stirring overnight, it was worked up routinely and submitted for preparative HPLC. The obtained carbamate was treated with lithium aluminun hydride (0.168 mmol) in THF at 80° C. for 1 hour. Afterwards the reaction mixture was concentrated to dryness under nitrogen stream, re-dissolved in methanol, and purified by preparative HPLC and then silica flash chromatography (10% methanol in CH2Cl2) to give 8.5 mg of the desired product as a free base. 1H NMR (500 MHz, CDCl3) δ ppm 1.42 (s, 3 H) 1.93 (m, 1 H) 2.09 (m, 1 H) 2.35 (s, 3 H) 2.37 (m, 1 H) 2.52 (m, 1 H) 3.54 (s, 2 H) 7.24 (m, 2 H) 7.34 (m, 4 H) 7.65 (s, 2 H) 7.76 (s, 1 H); 13C NMR (500 MHz, CDCl3) δ 144.64, 141.36, 131.68(q, JCCF=33.3 Hz), 128.45, 127.14, 126.65, 126.34, 123.39, (q, JCF=272.5 Hz), 121.4 (m), 80.33, 71.89, 47.16, 41.67, 38.03, 35.70, 22.76.

Workup

  1. customThe excess amount of borane was removed under nitrogen stream
  2. customThe residue was quenched further with methanol
  3. concentrationThe resultant solution was concentrated
  4. dissolutionre-dissolved in CH2Cl2
  5. washIt was washed with brine
  6. dry with materialdried with sodium sulfate
  7. concentrationAfter concentration
  8. concentrationAfterwards the reaction mixture was concentrated to dryness under nitrogen stream
  9. dissolutionre-dissolved in methanol
  10. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-2b4e33316a0c464291c07aeacb67d97e
Source dataset
uspto-grants-2007_02
Patent number
US07179926B2

Reaction notes

Loading…