Sodium hydride → HCID 90386045, compound

HRID 2274857Notes

Reaction equation

HRID 2274857 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([OH:9])[CH2:2]2.[H-].[Na+].[N:12]([C:15]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([CH3:26])=[CH2:25])[CH:19]=1)([CH3:17])[CH3:16])=[C:13]=[O:14]>C1COCC1>[CH2:25]=[C:24]([C:20]1[CH:19]=[C:18]([C:15]([NH:12][C:13](=[O:14])[O:9][C@@H:3]2[CH:4]3[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]3)[CH2:2]2)([CH3:17])[CH3:16])[CH:23]=[CH:22][CH:21]=1)[CH3:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 914043-Quinuclidinol, (-)-HCID 6041521-(1-Isocyanato-1-methylethyl)-3-(1-methylethenyl)benzene

Product 1

HCID 90386045HCID 90386045, compoundYield 95.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-quinuclidin-3-ol (194 mg, 1.52 mmol) in THF (5 mL) at room temperature was added NaH [60%, oil] (64 mg, 1.6 mmol). The reaction mixture was stirred for 15 min and 1-(2-isocyanatopropan-2-yl)-3-(prop-1-en-2-yl)benzene (302 uL, 1.53 mmol) was added dropwise. The reaction was stirred for a period of 30 min and quenched with brine. The solution was extracted with EtOAc and the organic layer was dried over Na2SO4 and concentrated. The crude material was purified on a combiflash (SiO2 cartridge, CHCl3 and 2N NH3 in MeOH) to afford the corresponding carbamate (475 mg, 95%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.49 (s, 1H), 7.31 (br s, 3H), 5.33 (s, 1H), 5.17 (s, 1H), 5.08 (s, 1H), 4.77-4.61 (m, 1H), 3.33-2.27 (m, 5H), 2.14 (s, 3H), 2.25-0.75 (m, 6H), 1.68 (br s, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 154.7, 147.2, 143.7, 141.6, 128.5, 124.2, 122.1, 112.8, 70.9, 55.7, 55.5, 47.5, 46.6, 32.2, 31.5, 29.9, 29.6, 25.5, 24.6, 22.9, 22.2, 19.6 ppm. Purity: 100% UPLCMS (210 nm); retention time 0.84 min; (M+1) 329.2. Anal. Calcd. for C20H28N2O2.0.06 (CHCl3): C, 71.59; H, 8.40; N, 8.58. Found: C, 71.51; H, 9.05; N, 8.60.

Workup

  1. stirringThe reaction was stirred for a period of 30 min
  2. customquenched with brine
  3. extractionThe solution was extracted with EtOAc
  4. dry with materialthe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude material was purified on a combiflash (SiO2 cartridge, CHCl3 and 2N NH3 in MeOH)

Sources & evidence

ORD record
ord-e3c19479518f47aa96128ab8a32d6663
Source dataset
uspto-grants-2015_09
Patent number
US09126993B2

Reaction notes

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