Sodium Chloride → HCID 69593328, compound

HRID 719599Notes

Reaction equation

HRID 719599 reaction equation
ClC(OCC(C)C)=O.CN1CCOCC1.[CH3:16][O:17][C:18](=[O:28])[C@H:19]([CH2:24][CH:25]([CH3:27])[CH3:26])[CH2:20][C:21]([OH:23])=O.[CH2:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][CH2:31][NH:30]1.[Cl-].[Na+]>ClCCl>[CH3:16][O:17][C:18](=[O:28])[CH:19]([CH2:20][C:21]([N:30]1[CH2:31][CH2:32][C:33]2[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:29]1)=[O:23])[CH2:24][CH:25]([CH3:27])[CH3:26]

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 70461,2,3,4-TetrahydroisoquinolineHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 5702633(R)-2-isobutylsuccinic acid-1-methyl ester

Product 1

HCID 69593328HCID 69593328, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
-15 °C

Procedure

iso-Butyl chloroformate (33.64 mg, 0.2463 mmol) in dichloromethane (2 ml) and N-methyl morpholine (49.83 mg, 0.4927 mmol) in dichloromethane (2 ml) were simultaneously added to a stirred solution of (R)-2-isobutyl succinic acid 1-methyl ester (42.15 mg, 0.2239 mmol) in dichloromethane (2 ml) at −15° C. under argon over 5 minutes. The mixture was stirred at −15° C. for 15 minutes. A freshly prepared solution of 1,2,3,4-tetrahydro-isoquinoline (29.83 mg, 0.2239 mmol) in dichloromethane (2 ml) and N-methylmorpholine (24.92 mg, 0.2463 mmol) was then added dropwise. The mixture was then stirred at ambient temperature for 16 hours. The reaction mixture was poured into saturated aqueous sodium chloride solution (1 ml). The aqueous layer was extracted with diethyl ether (2×5 ml) which was discarded. The aqueous layer was acidified with 1M hydrochloric acid to pH (12), then the product was extracted into dichloromethane (3×5 ml). The combined dichloromethane layers were washed with water (2×5 ml), saturated aqueous sodium chloride solution (2×5 ml) then dried (Na2SO4). The solvent was removed in vacuo to give a residue which was purified over silica gel eluting with a gradient of n-heptane:ethyl acetate 4:1. Desired fractions were combined and reduced in vacuo to leave 2-[2-(3,4-Dihydro-1H-isoquinolin-2-yl)-2-oxo-ethyl]-4-methyl-pentanoic acid methyl ester as a colourless oil (35 mg, 51.5% from starting acid). TLC (single UV spot, Rf=0.6, n-heptane:ethyl acetate 1:1), HPLC-MS (single UV peak with Rt=9.544 mins, 304.2 [M+H]+, 305.2 [M+2]+, 306.2 [M+3]+, 629.3 [2M+Na]+.

Workup

  1. stirringThe mixture was then stirred at ambient temperature for 16 hours
  2. extractionThe aqueous layer was extracted with diethyl ether (2×5 ml) which
  3. extractionthe product was extracted into dichloromethane (3×5 ml)
  4. washThe combined dichloromethane layers were washed with water (2×5 ml), saturated aqueous sodium chloride solution (2×5 ml)
  5. dry with materialthen dried (Na2SO4)
  6. customThe solvent was removed in vacuo
  7. customto give a residue which
  8. customwas purified over silica gel eluting with a gradient of n-heptane:ethyl acetate 4:1

Sources & evidence

ORD record
ord-e99c59044c8b4971942efafa72605f59
Source dataset
uspto-grants-2006_11
Patent number
US07132449B2

Reaction notes

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