Propargyl bromide → HCID 87404101, compound

HRID 588917Notes

Reaction equation

HRID 588917 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([OH:14])=[O:13])[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:18][C:19]#[CH:20]>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([OH:14])=[O:13])[CH2:10][O:11][C:18]#[C:19][CH3:20])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 98766N-[tert-butoxycarbonyl]-L-serine

Product 1

HCID 87404101HCID 87404101, compoundYield 101.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl L-serine 12 (25.42 g, 0.1239 mol) was dissolved in DMF (190 mL) and the solution cooled to 0° C. (ice bath). Sodium hydride (60% (w/w) dispersion in mineral oil, 10.90 g, 0.2725 mol) was added over 15 min and the reaction mixture stirred for 1 h at 0° C. 3-Bromopropyne (80% (w/w) solution in toluene, 20.25 g, 0.1362 mol) was added dropwise over 15 min. The reaction mixture was stirred for 1 h at 0° C., after which the ice bath was removed and stirring continued for 3 h 40 min at room temperature. The solvent was evaporated and the residue dissolved in H2O (800 mL). The solution was washed with Et2O (3×350 mL) and acidified to pH 2 by addition of 3 M HCl. The resulting mixture was extracted with EtOAc (5×350 mL). The combined organic extracts were dried with anhydrous MgSO4 and the solvent evaporated affording a yellow/orange viscous oil (30.51 g). A portion of the oil (8.70 g) was purified by flash column chromatography (eluent: EtOAc/hexane/AcOH (23:27:1)). The fractions containing reasonably pure compound by TLC (total volume: 950 mL) were washed with 0.5 M HCl (3×500 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a pale yellow, viscous oil (6.58 g, corresponds to 23.03 g from the given amounts of starting materials, 77%), with spectral characteristics in accordance with literature data10; 1H NMR (200 MHz, DMSO-d6) δ 12.62 (br s, 1H, COOH), 6.88 (d, J=8.2 Hz, 1H, NH (rotomer 1)), 6.53 (d, J=6.4 Hz, 1H, NH (rotomer 2)), 4.21-4.06 (m, 1H, CαH), 4.13 (d, J=2.4 Hz, 2H, CH2CCH), 3.66 (d, J=5.4 Hz, 2H, CH2), 3.40 (t, J=2.4 Hz, 1H, CCH), 1.38 (s, 9H, (CH3)3); 13C NMR (75 MHz, DMSO-d6) δ 171.8, 155.4, 79.9, 78.3, 77.4, 68.8, 57.7, 53.6, 28.2; HRMS (m/z): [M+Na]+ calcd. for C11H17NO5Na, 266.1004. found, 266.1010; Anal. Calcd. for C11H17NO5: C, 54.31; H, 7.04; N, 5.76. Found: C, 54.7; H, 7.1; N, 5.5.

Workup

  1. stirringThe reaction mixture was stirred for 1 h at 0° C.
  2. customafter which the ice bath was removed
  3. stirringstirring
  4. waitcontinued for 3 h 40 min at room temperature
  5. customThe solvent was evaporated
  6. dissolutionthe residue dissolved in H2O (800 mL)
  7. washThe solution was washed with Et2O (3×350 mL)
  8. additionacidified to pH 2 by addition of 3 M HCl
  9. extractionThe resulting mixture was extracted with EtOAc (5×350 mL)
  10. dry with materialThe combined organic extracts were dried with anhydrous MgSO4
  11. customthe solvent evaporated

Sources & evidence

ORD record
ord-e114a78b616e4ad8b77858c36c950f07
Source dataset
uspto-grants-2016_01
Patent number
US09227995B2

Reaction notes

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