Triphenylphosphine → 4-[2-(1,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl)-1-isopropyl-1H-indol-5-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 494007Notes

Reaction equation

HRID 494007 reaction equation
[O:1]=[S:2]1(=[O:23])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:11]([CH:20]([CH3:22])[CH3:21])[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([OH:19])=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34](O)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)(C)C)=O)=O)(C)(C)C>O1CCCC1>[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([O:19][C:15]2[CH:16]=[C:17]3[C:12](=[CH:13][CH:14]=2)[N:11]([CH:20]([CH3:21])[CH3:22])[C:10]([C:8]([N:5]2[CH2:4][CH2:3][S:2](=[O:1])(=[O:23])[CH2:7][CH2:6]2)=[O:9])=[CH:18]3)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 67073360(1,1-Dioxo-1lambda6-thiomorpholin-4-yl)-(5-hydroxy-1-isopropyl-1H-indol-2-yl)-methanone

Product 1

HCID 670734974-[2-(1,1-Dioxo-1lambda6-thiomorpholine-4-carbonyl)-1-isopropyl-1H-indol-5-yloxy]-piperidine-1-carboxylic acid tert-butyl esterYield 31.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold (0° C.) mixture of (1,1-dioxo-1λ6-thiomorpholin-4-yl)-(5-hydroxy-1-isopropyl-1H-indol-2-yl)-methanone (890 mg, 1.0 eq.), 1-tert-butyloxycarbonyl-4-hydroxy-piperidine (659 mg, 1.2 eq.) and triphenylphosphine (858 mg, 1.2 eq.) in tetrahydrofuran (6 mL) was added dropwise a solution of di-tert-butyl-azodicarboxylate (746 mg, 1.0 eq.) in tetrahydrofuran (4 mL). The reaction mixture was stirred for 15 h at room temperature, concentrated in vacuo, then purified on silica eluting with a gradient of cyclohexane/ethyl acetate. One fraction was isolated to yield 434 mg (31.6%) of the desired product as white oil. MS (m/e): 520.7 (MH+, 100%).

Workup

  1. concentrationconcentrated in vacuo
  2. custompurified on silica eluting with a gradient of cyclohexane/ethyl acetate
  3. customOne fraction was isolated

Sources & evidence

ORD record
ord-e2300664a39d487dbcbbf3a66e828f71
Source dataset
uspto-grants-2009_05
Patent number
US07538101B2

Reaction notes

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