Triethylamine → Methyl (2E)(4S)-6-{[3-(acetylamino)propyl]sulfonyloxy}-5,5-dimethyl-4-(1,1,2,2-tetramethyl-1-silapropoxy)hex-2-enoate

HRID 1671420Notes

Reaction equation

HRID 1671420 reaction equation
Cl[S:2]([CH2:5][CH2:6][CH2:7][NH:8][C:9](=[O:11])[CH3:10])(=[O:4])=[O:3].C(N(CC)CC)C.[OH:19][CH2:20][C:21]([CH3:38])([CH3:37])[C@@H:22]([O:29][Si:30]([CH3:36])([CH3:35])[C:31]([CH3:34])([CH3:33])[CH3:32])/[CH:23]=[CH:24]/[C:25]([O:27][CH3:28])=[O:26]>ClCCl.CN(C1C=CN=CC=1)C>[C:9]([NH:8][CH2:7][CH2:6][CH2:5][S:2]([O:19][CH2:20][C:21]([CH3:38])([CH3:37])[C@@H:22]([O:29][Si:30]([CH3:36])([CH3:35])[C:31]([CH3:32])([CH3:34])[CH3:33])/[CH:23]=[CH:24]/[C:25]([O:27][CH3:28])=[O:26])(=[O:4])=[O:3])(=[O:11])[CH3:10]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 10935552Methyl (2E)(4S)-6-hydroxy-5,5-dimethyl-4-(1,1,2,2-tetramethyl-1-silapropoxy)hex-2-enoateHCID 552792083-Acetamidopropane-1-sulfonyl chloride

Product 1

HCID 86628884Methyl (2E)(4S)-6-{[3-(acetylamino)propyl]sulfonyloxy}-5,5-dimethyl-4-(1,1,2,2-tetramethyl-1-silapropoxy)hex-2-enoateYield 55%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Following the general procedure for the preparation of neopentyl sulfonylester intermediates of Description 10, N-[3-(chlorosulfonyl)propyl]acetamide (9) (4.0 g, 19.8 mmol) in 40 mL of dichloromethane (DCM) in the presence of 1.2 g (9.8 mmol) of 4-(N,N-dimethylamino)pyridine (DMAP) and 2.8 mL (2.0 g, 19-8 mmol) of triethylamine (Et3N, TEA) was reacted at ca. 0° C. with 3.0 g (9.9 mmol) of methyl (2E)(4S)-6-hydroxy-5,5-dimethyl-4-(1,1,2,2-tetramethyl-1-silapropoxy)hex-2-enoate (4). After work-up and isolation, the crude material was purified by silica gel column chromatography using ethyl acetate (EtOAc) and methanol (MeOH) mixtures (EtOAc/MeOH=9:1) to provide 2.5 g (55% yield) the title compound (19a) as a colorless oil. Rf=0.46 (EtOAc). 1H NMR (400 MHz, CDCl3): δ=0.01 (s, 3H), 0.08 (s, 3H), 0.93 (s, 9H), 0.97 (s, 6H), 2.06 (s, 3H) 2.07-2.11 (m, 2H), 3.14-3.18 (m, 2H), 3.40-3.45 (m, 2H), 3.77 (s, 3H), 3.98 (d, J=9.6 Hz, 1H), 4.06 (d, J=9.2 Hz, 1H), 4.09 (dd, superimposed, J=6.4, 1.6 Hz, 1H), 5.93 (br., 1H), 5.96 (dd, J=15.6, 1H), 6.90 (dd, J=15.6, 6.4 Hz, 1H) ppm. MS (ESI) m/z 466.10 (M+H)+. The analytical data was consistent with the proposed structure.

Workup

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

Sources & evidence

ORD record
ord-3a507abe68b248f9b47d0b5d6461b5b4
Source dataset
uspto-grants-2011_08
Patent number
US07994218B2

Reaction notes

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