Methanol → Tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate

HRID 28815Notes

Reaction equation

HRID 28815 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]([C:24]2([OH:30])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=O)[CH:5]=[CH:6][CH:7]=1.B.CO>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]([C:24]2([OH:30])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:9][N:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15][CH2:16]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 6331BoraneHCID 68855385Tert-butyl 4-[(3-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate

Product 1

HCID 68852390Tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylateYield 98.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A solution of tert-butyl 4-[(3-bromophenyl)(1-hydroxycyclohexyl)acetyl]piperazine-1-carboxylate (2.12 g, 4.40 mmol) in dry tetrahydrofuran (10 mL) under nitrogen was treated dropwise with a solution of borane (1.0 M in tetrahydrofuran, 13.2 mL, 13.2 mmol). The resulting solution was heated at 70° C. for 2 h, after which time the reaction was cooled in an ice bath, treated dropwise with methanol (15 mL) and concentrated. The resulting viscous, colorless oil was re-dissolved in ethyl acetate (25 mL), washed with a saturated aqueous solution of sodium bicarbonate, water, brine, dried over sodium sulfate, filtered, and concentrated to give a white solid, which was purified via flash column chromatography (silica, gradient from 10% ethyl acetate/hexane to 20% ethyl acetate/hexane) to yield 2.02 g (98%) tert-butyl 4-[2-(3-bromophenyl)-2-(1-hydroxycyclohexyl)ethyl]piperazine-1-carboxylate as a white powder. MS (ESI) m/z 467/469 ([M+H]+); HRMS: calcd for C23H35BrN2O3, 466.1831; found (ESI), 467.1899; Anal. Calcd for C23H35BrN2O3: C, 59.10; H, 7.55; N, 5.99. Found: C, 59.14; H, 7.72; N, 5.77.

Workup

  1. temperatureafter which time the reaction was cooled in an ice bath
  2. concentrationconcentrated
  3. dissolutionThe resulting viscous, colorless oil was re-dissolved in ethyl acetate (25 mL)
  4. washwashed with a saturated aqueous solution of sodium bicarbonate, water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a white solid, which
  9. customwas purified via flash column chromatography (silica, gradient from 10% ethyl acetate/hexane to 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d0399a887f5349c09bf4bee576944719
Source dataset
uspto-grants-2008_09
Patent number
US07419980B2

Reaction notes

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