Isobutane → (3S,4R)-3-Hydroxymethyl-4-({isopropyl-[1-(3-methoxy-propyl)-1H-indole-6-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158408Notes

Reaction equation

HRID 1158408 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15]([C:17]2[CH:25]=[C:24]3[C:20]([CH:21]=[CH:22][N:23]3[CH2:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:19][CH:18]=2)=[O:16])[C@H:10]([C:34](C)(C)[O:35][SiH2]C(C)(C)C)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(C)(C)C.CC#N.O>CCOC(C)=O.CCOC(C)=O.CO.O.CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15]([C:17]2[CH:25]=[C:24]3[C:20]([CH:21]=[CH:22][N:23]3[CH2:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:19][CH:18]=2)=[O:16])[C@H:10]([CH2:34][OH:35])[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

9

Reactant 4

HCID 6360IsobutaneHCID 2724141Tetrabutylammonium FluorideHCID 18373917Acetonitrile--water (1/1)HCID 178495133tert-butyl (3S,4R)-3-(2-tert-butylsilyloxypropan-2-yl)-4-[[[1-(3-methoxypropyl)indole-6-carbonyl]-propan-2-ylamino]methyl]pyrrolidine-1-carboxylate

Product 1

HCID 68630543(3S,4R)-3-Hydroxymethyl-4-({isopropyl-[1-(3-methoxy-propyl)-1H-indole-6-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent2×HCID 21584119Ethylacetate methanolSolvent

Procedure

From (3S,4R)-3-(tert-butyl-dimethyl-silanyloxymethyl)-4-({isopropyl-[1-(3-methoxy-propyl)-1H-indole-6-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (6.79 g, 11.3 mmol) and TBAF (5.35 g, 17.0 mmol) and purification by flash chromatography on silivca gel (chexane/AcOEt 50:50 to 0:100 to AcOEt/MeOH 90:10). TLC, Rf (AcOEt)=0.34. MS (LC-MS): 432 [M+H-tBu]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/15 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 5.73 min.

Workup

  1. custom5.73 min.

Sources & evidence

ORD record
ord-58673269bf03418fa2e1db8a0b4a8a99
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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