Formaldehyde → 3-Benzyloxy-4-dimethylaminoestra-1,3,5(10)-trien-17-one

HRID 1003194Notes

Reaction equation

HRID 1003194 reaction equation
[CH2:1]([O:8][C:9]1[CH:26]=[CH:25][C:24]2[C@@H:23]3[C@H:14]([C@H:15]4[C@@:19]([CH2:21][CH2:22]3)([CH3:20])[C:18](=[O:27])[CH2:17][CH2:16]4)[CH2:13][CH2:12][C:11]=2[C:10]=1N)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:29]=O.[C:31]([BH3-])#[N:32].[Na+].[NH4+].[Cl-]>C1COCC1.CC#N>[CH2:1]([O:8][C:9]1[CH:26]=[CH:25][C:24]2[C@@H:23]3[C@H:14]([C@H:15]4[C@@:19]([CH2:21][CH2:22]3)([CH3:20])[C:18](=[O:27])[CH2:17][CH2:16]4)[CH2:13][CH2:12][C:11]=2[C:10]=1[N:32]([CH3:31])[CH3:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 25517Ammonium ChlorideHCID 5003444Sodium cyanoborohydride2×HCID 54424644HCID 54424644, compound

Product 1

HCID 693344893-Benzyloxy-4-dimethylaminoestra-1,3,5(10)-trien-17-oneYield 54%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3-benzyloxy-4-aminoestra-1,3,5(10)-trien-17-one (85, 0.188 g, 0.5 mmol) in THF (1.0 mL) and CH3CN (5.0 mL) were added 37% aqueous formaldehyde (1.0 mL) and sodium cyanoborohydride (0.251 g, 4.0 mmol); the mixture was then stirred for 3 h at room temperature. Additional sodium cyanoborohydride (0.251 g, 4.0 mmol) was then added, and the mixture stirred for 24 h. Saturated aqueous NH4Cl at 0° C. was added, and the mixture extracted with EtOAc. The combined organic layers were washed with H2O, saturated aqueous NaCl, and then dried (Na2SO4). The desiccant was filtered and the solvent was evaporated at reduced pressure. The residue was purified by column chromatography (silica gel) using n-hexane:EtOAc (3:1→1:1, v/v) to afford 0.109 g of 86 (54% yield).

Workup

  1. stirringthe mixture stirred for 24 h
  2. extractionthe mixture extracted with EtOAc
  3. washThe combined organic layers were washed with H2O, saturated aqueous NaCl
  4. dry with materialdried (Na2SO4)
  5. filtrationThe desiccant was filtered
  6. customthe solvent was evaporated at reduced pressure
  7. customThe residue was purified by column chromatography (silica gel)

Sources & evidence

ORD record
ord-f5cab91b97d5434da6ef93cc4e00ac87
Source dataset
uspto-grants-2000_04
Patent number
US06046186

Reaction notes

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