Hydrochloric Acid → 2-tert-butoxycarbonylamino-3-[3'-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-ylmethylsulfanyl]-propionic acid

HRID 1782683Notes

Reaction equation

HRID 1782683 reaction equation
C[O:2][C:3](=[O:43])[CH:4]([NH:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:5][S:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]3[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:31]([F:34])([F:33])[F:32])[CH:29]=4)[CH2:24][CH2:23][CH2:22]3)[CH:15]=2)=[CH:10][CH:9]=1.[OH-].[Na+].Cl>C1COCC1.CO>[C:39]([O:38][C:36]([NH:35][CH:4]([CH2:5][S:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]3[C:30]4[C:25](=[CH:26][CH:27]=[C:28]([C:31]([F:33])([F:34])[F:32])[CH:29]=4)[CH2:24][CH2:23][CH2:22]3)[CH:15]=2)=[CH:12][CH:13]=1)[C:3]([OH:43])=[O:2])=[O:37])([CH3:42])([CH3:40])[CH3:41]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 688198522-tert-butoxycarbonylamino-3-[3'-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-ylmethylsulfanyl]-propionic acid methyl ester

Product 1

HCID 115127442-tert-butoxycarbonylamino-3-[3'-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-ylmethylsulfanyl]-propionic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under a nitrogen atmosphere, a solution of 2-tert-butoxycarbonylamino-3-[3′-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-ylmethylsulfanyl]-propionic acid methyl ester (0.173 g, 0.281 mmol) in 4 mL of THF and 1 mL of methanol was treated with 2 N NaOH (1.5 mL, 2.81 mmol). After stirring at room temperature for 3 hours, the solution was acidified with 2 N HCl to a pH 3. The resulting solution was extracted with ethyl acetate (2×50 mL), dried over MgSO4 and concentrated. The resulting residue was purified by flash chromatography (5% methanol in dichloromethane) to afford 2-tert-butoxycarbonylamino-3-[3′-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-ylmethylsulfanyl]-propionic acid. 1H NMR (DMSO, 300 MHz) δ 7.58-7.49 (m, 4 H), 7.44-7.36 (m, 3 H), 7.21 (d, J=7.8 Hz, 1 H), 7.09 (d, J=7.5 Hz, 1 H), 6.76-6.70 (m, 2 H), 4.62 (s, 2 H), 4.14-4.07 (m, 1 H), 3.79 (s, 2 H), 3.47 (t, J=5.4 Hz, 2 H), 2.81-2.72 (m, 3 H), 1.99-1.91 (m, 1 H), 1.40 (s, 9 H); ESI-LCMS m/z calcd for C32H35F3N2O4S: 600.7; found 601.3 (M+1)+.

Workup

  1. extractionThe resulting solution was extracted with ethyl acetate (2×50 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe resulting residue was purified by flash chromatography (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-2a561daa93bc41678b94a936453b3b2f
Source dataset
uspto-grants-2009_03
Patent number
US07498356B2

Reaction notes

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