Formic Acid → Estrone sulfamate

HRID 1831860Notes

Reaction equation

HRID 1831860 reaction equation
C(O)=O.Cl[S:5]([N:8]=C=O)(=[O:7])=[O:6].[CH3:11][C@@:12]12[C:28](=[O:29])[CH2:27][CH2:26][C@H:25]1[C@H:24]1[C@@H:15]([C:16]3[CH:17]=[CH:18][C:19]([OH:30])=[CH:20][C:21]=3[CH2:22][CH2:23]1)[CH2:14][CH2:13]2>ClCCl.CN(C)C(=O)C>[S:5](=[O:6])(=[O:7])([O:30][C:19]1[CH:18]=[CH:17][C:16]2[C@@H:15]3[C@H:24]([C@H:25]4[C@@:12]([CH2:13][CH2:14]3)([CH3:11])[C:28](=[O:29])[CH2:27][CH2:26]4)[CH2:23][CH2:22][C:21]=2[CH:20]=1)[NH2:8]

Participants

6

Reactant 3

HCID 284Formic AcidHCID 5870EstroneHCID 70918Chlorosulfonyl isocyanate

Product 1

HCID 127676Estrone sulfamate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent2×

Procedure

A mixture of formic acid (284.92 mmol) and N,N-dimethyl acetamide (3.03 mmol) was added to a stirred solution of chlorosulfonyl isocyanate (277.47 mmol) in dichloromethane (87.5 ml) at 42° C. within a period of 3.5 hours. The mixture was heated to reflux for 15 minutes and cooled to ambient temperature. The resulting mixture was added to a stirred solution of estrone (184.93 mmol) in N,N-dimethyl acetamide (625 ml) at ambient temperature within a period of 20 minutes. The mixture was stirred at ambient temperature for 17 hours, and then poured onto water (1875 ml). After a while a white precipitate was formed. The suspension was stirred at ambient temperature for another 2 hours, and filtered. The crystals were washed twice with water (250 ml), and used without further drying and purification in the next step (Procedure II). Yield: 87.8 g (wet material) white crystals, purity (HPLC): 99.12%.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 15 minutes
  3. additionpoured onto water (1875 ml)
  4. customAfter a while a white precipitate was formed
  5. stirringThe suspension was stirred at ambient temperature for another 2 hours
  6. filtrationfiltered
  7. washThe crystals were washed twice with water (250 ml)
  8. customwithout further drying
  9. custompurification in the next step (Procedure II)

Sources & evidence

ORD record
ord-69bbe6a0941142198b371d0579f6692c
Source dataset
uspto-grants-2006_06
Patent number
US07067683B2

Reaction notes

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