Hydrochloric Acid → 2-{4-[2-tert-Butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid

HRID 720169Notes

Reaction equation

HRID 720169 reaction equation
C[O:2][C:3](=[O:46])[CH:4]([N:16]1[CH2:21][CH2:20][N:19]([C:22](=[O:40])[CH:23]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[CH:18]([CH2:41][CH:42]2[CH2:44][CH2:43]2)[C:17]1=[O:45])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.CO.[Li+].[OH-].Cl>C1COCC1.O>[C:36]([O:35][C:33]([NH:32][CH:23]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)[C:22]([N:19]1[CH2:20][CH2:21][N:16]([CH:4]([CH2:5][C:6]2[CH:15]=[CH:14][C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:7]=2)[C:3]([OH:46])=[O:2])[C:17](=[O:45])[CH:18]1[CH2:41][CH:42]1[CH2:44][CH2:43]1)=[O:40])=[O:34])([CH3:39])([CH3:37])[CH3:38]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 695873442-{4-[2-Tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methyl ester

Product 1

HCID 219015722-{4-[2-tert-Butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-{4-[2-tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-cyclopropylmethyl-2-oxo-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid methyl ester, 15, (531 mg, 0.842 mmol) in a mixture of THF (5 mL)/CH3OH (1 mL)/H2O (2 mL) is added LiOH (100 mg, 4.17 mmol). The reaction mixture is stirred for 4 hours, acidified with 1N HCl to pH 3 and extracted several times with EtOAc. The combined extracts are dried over Na2SO4, filtered, concentrated in vacuo and dried under high vacuum to give the free acid in quantitative yield, which is used directly without further purification. 1H NMR (300 MHz, CD3OD, Rotamers) δ 7.72–7.87 (m, 3H), 7.68 (s, 1H), 7.37–7.53 (m, 3H), 7.12–7.28 (m, 2H), 6.99–7.06 (m, 2H), 5.54–5.66 (m, 1H), 4.52–4.80 (m, 1.5H), 3.82–4.38 (m, 1.5H), 3.18–3.64 (m, 4H), 2.70–3.02 (m, 3H), 0.80–1.43 (m, 11H), −0.78–0.10 (m, 5H); 13C NMR (75 MHz, CD3OD, Rotamers) δ 171.68, 171.58, 170.23, 169.29, 167.86, 163.70, 156.08, 134.69, 134.57, 133.71, 133.14, 132.70, 131.26, 131.15, 130.73, 130.64, 128.19, 128.12, 127.55, 127.38, 127.29, 127.07, 126.12, 125.64, 79.61, 79.34, 58.68, 57.04, 56.18, 52.13, 51.65, 43.21, 42.29, 41.29, 38.61, 37.32, 37.21, 36.27, 34.23, 33.93, 27.50, 27.41, 6.45, 3.92, 3.66, 3.33; MS (ESMS) m/z 618.2 (M+H)+.

Workup

  1. extractionextracted several times with EtOAc
  2. dry with materialThe combined extracts are dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customdried under high vacuum
  6. customto give the free acid in quantitative yield, which
  7. customis used directly without further purification

Sources & evidence

ORD record
ord-d1610a52bcde422aad9ca6e3287d287b
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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