Methyl chloroformate → {(S)-6-[(R)-4-(4-Methoxycarbonyl-piperazin-1-ylmethyl)-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

HRID 1422622Notes

Reaction equation

HRID 1422622 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].[CH3:6][O:7][C:8](=[O:40])[CH2:9][C@H:10]1[C:14]2[CH:15]=[CH:16][C:17]([O:19][C@H:20]3[C:28]4[C:23](=[C:24]([CH2:33][N:34]5[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]5)[C:25]([C:29]([F:32])([F:31])[F:30])=[CH:26][CH:27]=4)[CH2:22][CH2:21]3)=[CH:18][C:13]=2[O:12][CH2:11]1.C(N(CC)CC)C>ClCCl>[CH3:6][O:7][C:8](=[O:40])[CH2:9][C@H:10]1[C:14]2[CH:15]=[CH:16][C:17]([O:19][C@H:20]3[C:28]4[C:23](=[C:24]([CH2:33][N:34]5[CH2:35][CH2:36][N:37]([C:2]([O:4][CH3:5])=[O:3])[CH2:38][CH2:39]5)[C:25]([C:29]([F:30])([F:31])[F:32])=[CH:26][CH:27]=4)[CH2:22][CH2:21]3)=[CH:18][C:13]=2[O:12][CH2:11]1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 90313619{(S)-6-[(R)-4-piperazin-1-ylmethyl-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

Product 1

HCID 90313521{(S)-6-[(R)-4-(4-Methoxycarbonyl-piperazin-1-ylmethyl)-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl chloroformate (11 μL) is added to a solution of {(S)-6-[(R)-4-piperazin-1-ylmethyl-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester (60 mg) and triethylamine (68 μL) in dichloromethane (2 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at room temperature for 2 h. Water is added and the resulting mixture is extracted with dichloromethane. The combined extracts are washed with brine and dried (Na2SO4). The solvent is evaporated and the residue is chromatographed on reversed phase (HPLC; acetonitrile/water) to give the title compound. LC (method 4): tR=0.99 min; Mass spectrum (ESI+): m/z=549 [M+H]+.

Workup

  1. temperaturechilled in an ice bath
  2. customThe cooling bath is removed
  3. additionWater is added
  4. extractionthe resulting mixture is extracted with dichloromethane
  5. washThe combined extracts are washed with brine
  6. dry with materialdried (Na2SO4)
  7. customThe solvent is evaporated
  8. customthe residue is chromatographed on reversed phase (HPLC; acetonitrile/water)

Sources & evidence

ORD record
ord-e2a986bf870d4db69900b2b633d32ee7
Source dataset
uspto-grants-2015_01
Patent number
US08927531B2

Reaction notes

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