Trifluoroacetic acid → [Ethoxy(4-phenylbutyl)phosphinyl]acetyl-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester

HRID 1156804Notes

Reaction equation

HRID 1156804 reaction equation
[CH2:1]([O:3][P:4]([CH2:16][C:17]([OH:19])=O)([CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:5])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.CC(C)(OC([N:38]1[C@H:46]([C:47]([O:49][CH2:50][O:51][C:52](=[O:57])[C:53]([CH3:56])([CH3:55])[CH3:54])=[O:48])[CH2:45][C:40]2([S:44][CH2:43][CH2:42][S:41]2)[CH2:39]1)=O)C.FC(F)(F)C(O)=O>C(#N)C>[CH2:1]([O:3][P:4]([CH2:16][C:17]([CH:43]1[CH2:42][S:41][C:40]2([CH2:45][CH:46]([C:47]([O:49][CH2:50][O:51][C:52](=[O:57])[C:53]([CH3:55])([CH3:54])[CH3:56])=[O:48])[NH:38][CH2:39]2)[S:44]1)=[O:19])([CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 13136848[Ethoxy(4-phenylbutyl)phosphoryl]acetic acidHCID 13136859(S)-7-[(1,1-Dimethylethoxy)carbonyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester

Product 1

HCID 86738446[Ethoxy(4-phenylbutyl)phosphinyl]acetyl-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid, (2,2-dimethyl-1-oxopropoxy)methyl esterYield 77.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1.7 g of [ethoxy(4-phenylbutyl)phosphinyl]acetic acid, acetonitrile and 0.96 g of carbonyldiimidazole is stirred under argon at 0° C. for 1 hour. (S)-7-[(1,1-Dimethylethoxy)carbonyl]-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester (2.5 g) is treated with trifluoroacetic acid (about 2 ml) and stirred at room temperature for 30 minutes. The trifluoroacetic acid is removed in vacuo, the residue taken up in acetonitrile and added dropwise to the above mixture over a 20 minute period at room temperature. After an additional 2.5 hours, the acetonitrile is stripped and the resulting oil is partitioned between ethyl acetate and water. The layers are separated and the organic portion is washed with 5% potassium sulfate, saturated sodium bicarbonate, brine, dried (MgSO4) and evaporated. The residue (3.4 g) is chromatographed on silica (120 g) eluting with ethyl acetate/dichloromethane (1:1) and yielding 2.7 g of the title compound as a glass.

Workup

  1. stirringstirred at room temperature for 30 minutes
  2. customThe trifluoroacetic acid is removed in vacuo
  3. additionadded dropwise to the above mixture over a 20 minute period at room temperature
  4. waitAfter an additional 2.5 hours
  5. customthe resulting oil is partitioned between ethyl acetate and water
  6. customThe layers are separated
  7. washthe organic portion is washed with 5% potassium sulfate, saturated sodium bicarbonate, brine
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe residue (3.4 g) is chromatographed on silica (120 g)
  11. washeluting with ethyl acetate/dichloromethane (1:1)

Sources & evidence

ORD record
ord-2c2a6f465c034bf393bfe3ceae2c17df
Source dataset
uspto-grants-1982_06
Patent number
US04337201

Reaction notes

Loading…