Hydrochloric Acid → (S)-1-[(2S,3R)-3-(tert-Butyl-diphenyl-silanyloxy)-2-((S)-2-{(E)-4-[2-((R)-1-hydroxy-ethyl)-quinolin-7-yl]-2,2-dimethyl-but-3-enoylamino}-3-methyl-butyrylamino)-butyryl]-hexahydro-pyridazine-3-carboxylic acid

HRID 2285383Notes

Reaction equation

HRID 2285383 reaction equation
ClC(Cl)(Cl)C[O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:66])[C@@H:14]([NH:35][C:36](=[O:65])[C@@H:37]([NH:41][C:42](=[O:64])[C:43]([CH3:63])([CH3:62])/[CH:44]=[CH:45]/[C:46]2[CH:55]=[C:54]3[C:49]([CH:50]=[CH:51][C:52]([C@H:56]([O:58]C(=O)C)[CH3:57])=[N:53]3)=[CH:48][CH:47]=2)[CH:38]([CH3:40])[CH3:39])[C@H:15]([O:17][Si:18]([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH3:16])[NH:8]1)=[O:6].O.[OH-].[Li+].Cl>O1CCCC1.O>[C:31]([Si:18]([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[O:17][C@H:15]([CH3:16])[C@H:14]([NH:35][C:36](=[O:65])[C@@H:37]([NH:41][C:42](=[O:64])[C:43]([CH3:62])([CH3:63])/[CH:44]=[CH:45]/[C:46]1[CH:55]=[C:54]2[C:49]([CH:50]=[CH:51][C:52]([C@H:56]([OH:58])[CH3:57])=[N:53]2)=[CH:48][CH:47]=1)[CH:38]([CH3:40])[CH3:39])[C:13]([N:9]1[CH2:10][CH2:11][CH2:12][C@@H:7]([C:5]([OH:6])=[O:4])[NH:8]1)=[O:66])([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 86709673(S)-1-[(2S,3R)-2-((S)-2-{(E)-4-[2-((R)-1-Acetoxy-ethyl)-quinolin-7-yl]-2,2-dimethyl-but-3-enoylamino}-3-methyl-butyrylamino)-3-(tert-butyl-diphenyl-silanyloxy)-butyryl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester

Product 1

HCID 86709672(S)-1-[(2S,3R)-3-(tert-Butyl-diphenyl-silanyloxy)-2-((S)-2-{(E)-4-[2-((R)-1-hydroxy-ethyl)-quinolin-7-yl]-2,2-dimethyl-but-3-enoylamino}-3-methyl-butyrylamino)-butyryl]-hexahydro-pyridazine-3-carboxylic acidYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-1-[(2S,3R)-2-((S)-2-{(E)-4-[2-((R)-1-Acetoxy-ethyl)-quinolin-7-yl]-2,2-dimethyl-but-3-enoylamino}-3-methyl-butyrylamino)-3-(tert-butyl-diphenyl-silanyloxy)-butyryl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (444 mg, 0.440 mmol) was taken up in a mixture of tetrahydrofuran (10 mL) and water (3 mL) and cooled using an ice bath. Lithium hydroxide monohydrate (148 mg, 3.52 mmol) was then added and the reaction was allowed to slowly warm to room temperature and left to stir for eighty minutes. The solution was then neutralised with hydrochloric acid (2 M) and concentrated until all volatiles had been removed to afford the title compound (368 mg, 100%) as a yellow solid. 1H NMR (300 MHz, CD3OD) δ 0.83 (d, J=6.5 Hz, 3H), 0.87-93 (m, 7H), 0.96 (s, 9H), 1.16-1.61 (m, 13H), 1.63-1.81 (m, 2H), 2.10-2.23 (m, 2H), 2.26-2.33 (m, 1H), 2.64-2.76 (m, 1H), 3.98-4.21 (m, 3H), 4.86 (d, J=11.8 Hz, 1H), 5.08 (d, J=9.6 Hz, 1H), 6.81 (ABq, Δδ=0.17, JAB=16.2 Hz, 2H), 7.13-7.19 (m, 1H), 7.22-7.29 (m, 1H), 7.32-7.47 (m, 6H), 7.52-7.63 (m, 4H), 7.72-8.12 (m, 3H). LCMS (m/z) 836.6 [M+H], Tr=3.03 min.

Workup

  1. temperaturecooled
  2. waitleft
  3. concentrationconcentrated until all volatiles
  4. customhad been removed

Sources & evidence

ORD record
ord-3dfafefaf487482d9f7269fb4eca33a4
Source dataset
uspto-grants-2015_09
Patent number
US09145441B2

Reaction notes

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