Sodium hydride → HCID 131733410, compound

HRID 2274885Notes

Reaction equation

HRID 2274885 reaction equation
[N:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[C@H:3]([OH:8])[CH2:2]2.[H-].[Na+].[N:11]([C:14]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([CH3:25])=[CH2:24])[CH:18]=1)([CH3:16])[CH3:15])=[C:12]=[O:13]>C1COCC1>[N:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[C@H:3]([O:8][C:12](=[O:13])[NH:11][C:14]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([CH3:25])=[CH2:24])[CH:18]=1)([CH3:16])[CH3:15])[CH2:2]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6041521-(1-Isocyanato-1-methylethyl)-3-(1-methylethenyl)benzeneHCID 14453849HCID 14453849, compound

Product 1

HCID 131733410HCID 131733410, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (+/−)-(3S,4S)-1-azabicyclo[2.2.1]heptan-3-ol (294 mg, 2.6 mmol) in THF (5 mL) at room temperature was added NaH [60%, oil] (107 mg, 2.67 mmol). The reaction mixture was stirred for 15 min and 1-(2-isocyanatopropan-2-yl)-3-(prop-1-en-2-yl)benzene (344 uL, 1.73 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 as a clear oil (140 mg, 26%). 1H NMR (400 MHz, CDCl3) δ 7.26-7.20 (m, 3H), 7.11 (m, 1H), 5.18 (s, 1H), 5.19 (br s, 1H), 5.01 (s, 1H), 4.81 (br s, 1H), 2.99 (br s, 1H), 2.82(br s, 1H), 2.70 (br s, 1H), 2.53 (br s, 2H), 2.33 (br s, 1H), 2.02 (s, 3H), 1.76 (br s, 1H) 1.61 (br s, 6H), 1.52 (br s, 1H), 1.37 (br s, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 147.1, 143.7, 141.5, 128.5, 124.1, 122.1, 112.7, 75.6, 60.6, 59.4, 55.4, 54.3, 53.9, 41.5, 29.9, 29.8, 29.4, 22.2, 21.6 ppm. Purity: >98% UPLCMS (210 nm); retention time 0.83 min; (M+1) 315

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-af5c513c7dcc49fca77b27ce8f3eaf71
Source dataset
uspto-grants-2015_09
Patent number
US09126993B2

Reaction notes

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