o-Phenylbenzoic acid → HCID 18387431, compound

HRID 2296753Notes

Reaction equation

HRID 2296753 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[S:5][C:6]2[CH:23]=[CH:22][CH:21]=[CH:20][C:7]=2[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=2)[C:9](=[O:11])[CH:10]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[C:36]1([C:42]2[CH:50]=[CH:49][CH:48]=[CH:47][C:43]=2[C:44](Cl)=[O:45])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C1(C2C=CC=CC=2)C(C(O)=O)=CC=CC=1>C1COCC1.O>[OH:1][CH2:2][CH2:3][C:4]1[S:5][C:6]2[CH:23]=[CH:22][CH:21]=[CH:20][C:7]=2[N:8]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([NH:19][C:44](=[O:45])[C:43]3[CH:47]=[CH:48][CH:49]=[CH:50][C:42]=3[C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[CH:17][CH:18]=2)[C:9](=[O:11])[CH:10]=1

Participants

7

Reactant 4

HCID 70357o-Phenylbenzoic acidHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 12563768[1,1'-Biphenyl]-2-carbonyl chlorideHCID 18387440HCID 18387440, compound

Product 1

HCID 18387431HCID 18387431, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a cold (ice-bath) solution of 2-(2-hydroxyethyl)-5-(4-aminobenzyl)-1,5-benzothiazepine-4-one as prepared in Example 21 (0.865 g, 2.6 mM) in dry THF was added N,O-bis(trimethylsilyl)acetamide (1.16 ml, 5.2 mM). After 1 hour, 2-phenylbenzoyl chloride (0.570 g, 2.6 mM), prepared from 2-biphenylcarboxylic acid as described in Example 3, was added and stirring was continued for an addition hour. Water (80 ml) was added and the mixture was extracted with ethyl acetate (2×80 ml). The organic extract was dried (MgSO4), filtered and evaporated in vacuo to give a crude product. Purification by flash column chromatography (EM silica gel 60; 30% EtOAc in CH2Cl2) yielded the desired product as a white solid (1.1 g, 83%) m.p.116-120° C. 1H NMR (300 MHz, DMSOd6) δ7.8 (d, J=7 Hz, 1H); 5.09(d, J=15 Hz, H); 4.89(d,J=15 Hz,1H); 3.79 (m, 3H); 2.69-2.24(m, 2H); 1.71 (m, 2H); m/z (MH+)509.

Workup

  1. additionwas added
  2. additionwas continued for an addition hour
  3. extractionthe mixture was extracted with ethyl acetate (2×80 ml)
  4. extractionThe organic extract
  5. dry with materialwas dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customto give a crude product
  9. customPurification by flash column chromatography (EM silica gel 60; 30% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-e89c51fcff88484b8c00ce3448989f65
Source dataset
uspto-grants-2002_12
Patent number
US06489321B1

Reaction notes

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