Triethylamine → HCID 178473650, compound

HRID 1919457Notes

Reaction equation

HRID 1919457 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:23][CH2:24][CH3:25])=[O:22])=[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:23][CH2:24][CH3:25])=[O:22])=[O:16])(=[O:10])=[O:9])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 75654Diphenyl chlorophosphateHCID 54755652HCID 54755652, compound

Product 1

HCID 178473650HCID 178473650, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Following the general procedure for phosphorylation of Description 23, (ethoxycarbonyloxy)ethyl (2R)-4-{[3-(acetylamino)propyl]sulfonyloxy}-3,3-dimethyl-2-hydroxy-butanoate (32) (0.43 g, 1.0 mmol) dissolved in 10 mL of anhydrous dichloromethane (DCM) was reacted with 0.58 mL (0.67 g, 2.5 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) (0.35 mL, 0.25 g, 2.5 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 0.43 g (65% yield) of the title compound (51a) as a colorless oil. Rf=0.45 (EtOAc). 1H NMR (400 MHz, CDCl3, both diastereomers): δ=1.09-1.10 (2s, 3H), 1.12-1.13 (2s, 3H), 1.26-1.32 (m, 3H), 1.45-1.52 (2d, J=5.6, 5.6 Hz, 3H), 1.86-1.87 (2s, 3H), 2.01-2.06 (m, 2H), 3.15-3.17 (m, 2H), 3.39-3.34 (m, 2H), 3.98-4.05 (m, 2H), 4.15-4.22 (m, 3H), 4.87-4.91 (2d, J=7.6, 7.6 Hz, 1H), 6.30-6.34 (br. m, 1H), 6.81-6.83 (m, 1H), 7.18-7.26 (m, 6H), 7.33-7.38 (m, 4H) ppm. MS (ESI) m/z 660.11 (M+H)+, 681.94 (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-86eb1fe9812443ad93d2b199990271e7
Source dataset
uspto-grants-2012_05
Patent number
US08168617B2

Reaction notes

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