Diisopropylethylamine → HCID 66654975, compound

HRID 2036205Notes

Reaction equation

HRID 2036205 reaction equation
[CH:1]([C@@H:4]1[CH2:6][C@H:5]1[C:7]([OH:9])=O)([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.C([O:44][C:45](=[O:65])[CH2:46][O:47][C:48]1[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][C:49]=1[C@@H:55]1[C:64]2[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=2)[CH2:58][CH2:57][NH:56]1)C>CN(C=O)C.C(O)=O>[Cl:54][C:51]1[CH:52]=[CH:53][C:48]([O:47][CH2:46][C:45]([OH:65])=[O:44])=[C:49]([C@@H:55]2[C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[CH2:58][CH2:57][N:56]2[C:7]([C@@H:5]2[CH2:6][C@H:4]2[CH:1]([CH3:2])[CH3:3])=[O:9])[CH:50]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 596179281355058-91-1HCID 66653910HCID 66653910, compound

Product 1

HCID 66654975HCID 66654975, compound

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (±)-trans-2-isopropyl-cyclopropanecarboxylic acid (39 mg, 0.31 mmol, 1.3 eq.) in DMF (2 mL), DIPEA (4 eq.) and TBTU (98 mg, 0.31 mmol, 1.3 eq.) were added in sequence. The resulting solution was stirred at r.t. for 30 min. ((S)-4-Chloro-2-1,2,3,4-tetrahydro-isoquinolin-1-yl-phenoxy)-acetic acid ethyl ester hydrochloride (90 mg, 0.24 mmol, 1.0 eq.) was added and the resulting mixture was stirred at r.t. for 18 hours. The solution was neutralized with formic acid (1 mL) and then purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo (Genevac). To a solution of the ethyl ester derivative in DMF (1 mL), 1M aq. NaOH (0.5 mL) was added. The mixture was stirred at r.t. for 18 hours. The solution was neutralized with formic acid (1 mL) and then purified by prep. HPLC (column: Waters XBridge, 19×50 mm, 5 um, UV/MS, acidic conditions) and concentrated in vacuo (Genevac) to give {4-Chloro-2-[(S)-2-(trans-2-isopropyl-cyclopropanecarbonyl)-1,2,3,4-tetrahydro-isoquinolin-1-yl]-phenoxy}-acetic acid (diastereoisomer 1) (LC-MS 1FA: tR=1.13 min; [M+H]+=428.3) and {4-Chloro-2-[(S)-2-(trans-2-isopropyl-cyclopropanecarbonyl)-1,2,3,4-tetrahydro-isoquinolin-1-yl]-phenoxy}-acetic acid (diastereoisomer 2) (LC-MS 1FA: tR=1.15 min; [M+H]+=428.3)

Workup

  1. additionwas added
  2. custompurified by prep
  3. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo (Genevac)
  4. additionTo a solution of the ethyl ester derivative in DMF (1 mL), 1M aq. NaOH (0.5 mL) was added
  5. stirringThe mixture was stirred at r.t. for 18 hours
  6. custompurified by prep
  7. concentrationHPLC (column: Waters XBridge, 19×50 mm, 5 um, UV/MS, acidic conditions) and concentrated in vacuo (Genevac)

Sources & evidence

ORD record
ord-184e98ce391447539d6ba798b8982a74
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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