Water → HCID 178521363, compound

HRID 1018388Notes

Reaction equation

HRID 1018388 reaction equation
[CH2:1]([O:8][C:9](=[O:34])[C:10]1[CH:15]=[C:14]([NH:16][C:17](=[O:33])[CH2:18][C:19](=[O:32])[CH2:20][O:21][C:22]23[CH2:31][CH:26]4[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]4)[CH2:23]2)[CH2:29]3)[CH:13]=[CH:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[N:36]([O-])=[O:37].[Na+]>C(O)(=O)C.C1COCC1>[CH2:1]([O:8][C:9](=[O:34])[C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([NH:16][C:17](=[O:33])[C:18](=[N:36][OH:37])[C:19](=[O:32])[CH2:20][O:21][C:22]23[CH2:29][CH:28]4[CH2:27][CH:26]([CH2:25][CH:24]([CH2:30]4)[CH2:23]2)[CH2:31]3)[CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 962WaterHCID 23668193Sodium NitriteHCID 54265492HCID 54265492, compound

Product 1

HCID 178521363HCID 178521363, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of the product of step b (2.10 g, 4.55 mmol) in acetic acid (20 ml) and THF (20 ml) was added water (2 ml). The mixture was cooled to 5° C. and an aqueous solution (3 ml) of sodium nitrite (0.41 g, 5.92 mmol) was added dropwise while maintaining the temperature below 10° C. Upon completion of the addition, the reaction mixture was allowed to warm to room temperature and stirred for 1 h. The THF and acetic acid were removed in vacuo and the solution was partitioned between water (100 ml) and ethyl acetate (100 ml). 1M NaOH was added until pH 8 was reached, the layers were separated, and the aqueous layer was washed with ethyl acetate (20 ml). The combined organic layers were washed with brine (100 ml), dried (MgSO4) and the solvent was evaporated to yield a yellow oil (2.13 g, 96%). The crude product was purified by flash column chromatography (silica, DCM/ethyl acetate 95:5) to afford a yellow foam (1.29 g, 58%). 1H NMR (300 MHz, CDCl3) 11.04 (1H, br s), 8.23 (1H, s), 7.94 (1H, d), 7.86 (1H, d), 7.50-7.36 (6H, m), 5.39 (2H, s), 4.82 (2H, s), 2.20 (3H, br s), 1.81 (6H, s), 1.65 (6H, m).

Workup

  1. temperaturewhile maintaining the temperature below 10° C
  2. additionUpon completion of the addition
  3. temperatureto warm to room temperature
  4. customThe THF and acetic acid were removed in vacuo
  5. customthe solution was partitioned between water (100 ml) and ethyl acetate (100 ml)
  6. addition1M NaOH was added until pH 8
  7. customthe layers were separated
  8. washthe aqueous layer was washed with ethyl acetate (20 ml)
  9. washThe combined organic layers were washed with brine (100 ml)
  10. dry with materialdried (MgSO4)
  11. customthe solvent was evaporated

Sources & evidence

ORD record
ord-f24878d8368c4cad80d0d0988982aff7
Source dataset
uspto-grants-2002_11
Patent number
US06479531B1

Reaction notes

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