Trifluoroacetic acid → HCID 14011750, compound

HRID 986212Notes

Reaction equation

HRID 986212 reaction equation
FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1.[CH2:16]([O:18][C:19]([CH:21]([NH:30][C@H:31]1[CH2:36][S:35][CH:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:33]([CH2:43][C:44]([O:46]CC[Si](C)(C)C)=[O:45])[C:32]1=[O:53])[CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:20])[CH3:17]>C(Cl)Cl>[CH2:16]([O:18][C:19]([CH:21]([NH:30][C@H:31]1[CH2:36][S:35][CH:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:33]([CH2:43][C:44]([OH:46])=[O:45])[C:32]1=[O:53])[CH2:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:20])[CH3:17]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 14011748HCID 14011748, compound

Product 1

HCID 14011750HCID 14011750, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of trifluoroacetic acid (8 ml.) and anisole (0.4 ml.) is cooled in an ice-water bath under nitrogen and treated with (5R)-5[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]dihydro-4-oxo-2-phenyl-2H-1,3-thiazine-3(4H)-acetic acid, 2-(trimethylsilyl)ethyl ester (B-slow isomer) (400 mg., 0.72 mmole) dissolved in dry methylene chloride (4 ml.). The cooling bath is removed and the reaction is stirred at ambient temperature for 3 hours, then concentrated in vacuo and azeotroped with toluene. The crude product (440 mg.) is chromatographed on 150 ml. of HP-20 eluted with a gradient from 400 ml. of water:acetonitrile (5:4) to 400 ml. of 100% acetonitrile. The product containing fractions are pooled, evaporated, then precipitated from ethanol (10 ml.) by the addition of water (300 ml.). By this method 171 mg. of (5R)-5-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]dihydro-4-oxo-2-phenyl-2H1,3-thiazine-3(4H)-acetic acid (B-slow isomer) are obtained; m.p. 130°-135°; [α]D =-36.1° (c=1, methanol). TLC (ethyl acetate:pyridine:acetic acid: water; 100:20:6:11) spot at Rf =0.79.

Workup

  1. temperatureis cooled in an ice-water bath under nitrogen
  2. customThe cooling bath is removed
  3. concentrationconcentrated in vacuo
  4. customazeotroped with toluene
  5. customThe crude product (440 mg.) is chromatographed on 150 ml
  6. washof HP-20 eluted with a gradient from 400 ml
  7. additionThe product containing fractions
  8. customevaporated
  9. customprecipitated from ethanol (10 ml.) by the addition of water (300 ml.)

Sources & evidence

ORD record
ord-ac78906559dc4c3481772c1c21425bc1
Source dataset
uspto-grants-1987_12
Patent number
US04711884

Reaction notes

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