Triethylamine → 2-(4-Nitro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester

HRID 387230Notes

Reaction equation

HRID 387230 reaction equation
[C:1]([O:5][C:6](=[O:23])[N:7]([CH2:20][CH2:21][OH:22])[CH2:8][CH:9](O)[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:7]1[CH2:20][CH2:21][O:22][CH:9]([C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=2)[CH2:8]1)=[O:23])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 67119617Tert-butyl N-[2-hydroxy-2-(4-nitrophenyl)ethyl]-N-(2-hydroxyethyl)carbamate

Product 1

HCID 671197592-(4-Nitro-phenyl)-morpholine-4-carboxylic acid tert-butyl esterYield 68.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To an ice-cold stirred mixture of (2-hydroxyethyl)-[2-hydroxy-2-(4-nitro-phenyl)-ethyl]-carbamic acid tert-butyl ester (5.50 g, 16.8 mmol) and triphenylphosphine (5.17 g, (19.7 mmol) in toluene (80 mL) was added triethylamine (6.15 mL, 4.46 g, 44.2 mmol) followed a solution of di-tert-butylazodicarboxylate (3.10 mL, 19.7 mmol) in toluene (30 mL) dropwise. The reaction mixture was stirred for 18 h at room temperature, washed with water (50 mL), and the aqueous layer was back extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated. The residue was purified by column chromatography eluting with dichloromethane, the obtained product was triturated with diisopropyl ether and collected. The title compound (3.56 g, 11.5 mmol, 68%) was obtained as a white solid. ESMS m/z 253 (M+H-tBu)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.23 (d, J=8.3 Hz, 2H) 7.57 (d, J=8.3 Hz, 2H) 4.53 (d, J=10.3 Hz, 1H) 4.20 (br. s., 1H) 4.06 (d, J=11.3 Hz, 1H) 3.94 (br. s., 1H) 3.66-3.75 (m, 1H) 3.06 (br. s., 1H) 2.76 (br. s., 1H) 1.50 (s, 9H).

Workup

  1. washwashed with water (50 mL)
  2. extractionthe aqueous layer was back extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography
  7. washeluting with dichloromethane
  8. customthe obtained product was triturated with diisopropyl ether
  9. customcollected

Sources & evidence

ORD record
ord-9e5650bb366245e991ab304e85b228c7
Source dataset
uspto-grants-2013_02
Patent number
US08372970B2

Reaction notes

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