Triethylamine → HCID 178474820, compound

HRID 1919456Notes

Reaction equation

HRID 1919456 reaction equation
[C:1]([NH:4][CH2:5][CH2:6][CH2:7][S:8]([O:11][CH2:12][C:13]([CH3:28])([CH3:27])[C@@H:14](O)[C:15]([O:17][CH2:18][CH2:19][O:20][C:21](=[O:25])[CH:22]([CH3:24])[CH3:23])=[O:16])(=[O:10])=[O:9])(=[O:3])[CH3:2].[P:29](Cl)(OC1C=CC=CC=1)([O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:30].C(N(CC)CC)C>ClCCl.CN(C1C=CN=CC=1)C>[C:1]([NH:4][CH2:5][CH2:6][CH2:7][S:8]([O:11][CH2:12][C:13]([CH3:28])([CH3:27])[C@@H:14]([PH:29]([O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:30])[C:15]([O:17][CH2:18][CH2:19][O:20][C:21](=[O:25])[CH:22]([CH3:24])[CH3:23])=[O:16])(=[O:10])=[O:9])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 75654Diphenyl chlorophosphateHCID 25225743HCID 25225743, compound

Product 1

HCID 178474820HCID 178474820, compoundYield 91%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Following the general procedure for phosphorylation of Description 23, (2-methylpropanoyloxy)ethyl (2R)-4-{[3-(acetylamino)propyl]sulfonyloxy}-3,3-dimethyl-2-hydroxy-butanoate (29) (1.0 g, 2.4 mmol) dissolved in 20 mL of anhydrous dichloromethane (DCM) was reacted with 1.46 mL (1.9 g, 7.0 mmol) of diphenyl chlorophosphate [(PhO)2POCl] in the presence of 4-(N,N-dimethylamino)pyridine (DMAP) (0.17 g, 1.4 mmol) and triethylamine (TEA) (0.97 mL, 0.71 g, 7.0 mmol). The reaction was monitored by TLC. After aqueous work-up, the crude material was further purified by silica gel column chromatography using ethyl acetate (EtOAc) as eluent to provide 1.2 g (80% yield) of the title compound (49a) as a colorless oil. Rf=0.55 (EtOAc). 1H NMR (400 MHz, CDCl3, both diastereomers): δ=1.06-1.15 (m, 12H), 1.40-1.46 (2d, J=5.6, 5.6 Hz, 3H), 1.85 (s, 3H), 2.01-2.08 (m, 2H), 2.45-2.55 (m, 1H), 3.13-3.17 (m, 2H), 3.28-3.33 (m, 2H), 3.97-4.04 (m, 2H), 4.84-4.88 (2d, J=7.2, 7.6 Hz, 1H), 6.32-6.36 (br. m, 1H), 6.88-6.93 (m, 1H), 7.18-7.26 (m, 6H), 7.31-7.38 (m, 4H) ppm. MS (ESI) m/z 658.25 (M+H)+. The analytical data was consistent with proposed structure.

Workup

  1. customAfter aqueous work-up, the crude material was further purified by silica gel column chromatography

Sources & evidence

ORD record
ord-eec9a8b36e844c5eaed294db9141fbaf
Source dataset
uspto-grants-2012_05
Patent number
US08168617B2

Reaction notes

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