Triethylamine → HCID 178474821, compound

HRID 1919458Notes

Reaction equation

HRID 1919458 reaction equation
[C:1]([NH:4][CH2:5][CH2:6][CH2:7][S:8]([O:11][CH2:12][C:13]([CH3:29])([CH3:28])[C@@H:14](O)[C:15]([O:17][CH2:18][CH2:19][O:20][C:21]([O:23][CH:24]([CH3:26])[CH3:25])=[O:22])=[O:16])(=[O:10])=[O:9])(=[O:3])[CH3:2].[P:30](Cl)(OC1C=CC=CC=1)([O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:31].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]([CH3:29])([CH3:28])[C@@H:14]([PH:30]([O:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:31])[C:15]([O:17][CH2:18][CH2:19][O:20][C:21]([O:23][CH:24]([CH3:26])[CH3:25])=[O:22])=[O:16])(=[O:10])=[O:9])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 75654Diphenyl chlorophosphateHCID 25225744HCID 25225744, compound

Product 1

HCID 178474821HCID 178474821, compoundYield 97.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Following the general procedure for phosphorylation of Description 23, (methylethoxycarbonyloxy)ethyl (2R)-4-{[3-(acetylamino)propyl]sulfonyloxy}-3,3-dimethyl-2-hydroxy-butanoate (40) (0.88 g, 2.0 mmol) dissolved in 10 mL of anhydrous dichloromethane (DCM) was reacted with 0.58 mL (1.6 g, 6.0 mmol) of diphenyl chlorophosphate [(PhO)2POCl] in the presence of 4-(N,N-dimethylamino)pyridine (DMAP) (0.12 g, 1.0 mmol) and triethylamine (TEA) (0.84 mL, 0.61 g, 6.0 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 1.1 g (81% yield) of the title compound (52a) as a colorless oil. Rf=0.45 (EtOAc). 1H NMR (400 MHz, CDCl3, both diastereomers): δ=1.08-1.09 (2s, 3H), 1.12-1.13 (2s, 3H), 1.25-1.32 (m, 6H), 1.44-1.50 (2d, J=5.6, 5.6 Hz, 3H), 1.85 (s, 3H), 1.99-2.06 (m, 2H), 3.13-3.18 (m, 2H), 3.28-3.32 (m, 2H), 3.98-4.05 (m, 2H), 4.82-4.91 (m, 2H), 6.38-6.42 (br. m, 1H), 6.79-6.85 (m, 1H), 7.15-7.23 (m, 6H), 7.30-7.38 (m, 4H) ppm. MS (ESI) m/z 674.19 (M+H)+, 696.09 (M+Na)+. The analytical data was consistent with the proposed structure.

Workup

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

Sources & evidence

ORD record
ord-f5fa464799574a7c8b9389b60ecd06f6
Source dataset
uspto-grants-2012_05
Patent number
US08168617B2

Reaction notes

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