Divinyl sulfone → 1,1-Dimethylethyl N-((1S)-2-(methoxymethylamino)-2-oxo-1-(phenylmethyl)ethyl)carbamate

HRID 2111530Notes

Reaction equation

HRID 2111530 reaction equation
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10](O)=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.CNOC.C(S(C=C)(=O)=O)=C.[NH:32]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[C@H:33]([C:41]([N:43]([CH3:46])[O:44][CH3:45])=[O:42])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[NH:32]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[C@H:33]([C:41]([N:43]([CH3:46])[O:44][CH3:45])=[O:42])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[C:16]([O:15][C:13]([NH:1][CH:2]([CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[CH:10]=[O:11])=[O:14])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 5

HCID 6496Divinyl sulfoneHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 110559451,1-Dimethylethyl N-((1S)-2-(methoxymethylamino)-2-oxo-1-(phenylmethyl)ethyl)carbamateHCID 21226445Aluminium lithium hydride

Product 2

HCID 5463171,1-Dimethylethyl N-(1-formyl-2-phenylethyl)carbamateHCID 110559451,1-Dimethylethyl N-((1S)-2-(methoxymethylamino)-2-oxo-1-(phenylmethyl)ethyl)carbamateYield 93%

Procedure

Boc-Phe-N(OCH3)CH3 was prepared from Boc-Phe-OH and N,O-dimethylhydroxylamine hydrochloride using standard mixed anhydride coupling procedure, yield 93%. 1H-NMR (CDCl3) δ 1.4 (s, 9H, Boc), 2.8-2.9 (m, 1H, CH2-Phe), 3.0-3.1 (m, 1H, CH2-Phe), 3.2 (s, 3H, N—CH3), 3.6 (s, 3H, O—CH3), 4.9 (m, 1H, α-H), 5.2 (b, 1H, NH), 7.1-7.3 (m, 5H, Ph). MS (FAB+) m/z 309 (M+1, 30%), 253 (M−tBu+1, 100%). Reduction of Boc-Phe-N(OCH3)CH3 with lithium aluminum hydride according to a previous method described in J. A. Fehrentz et al., Synthesis (1983), 8, 676 gave Boc-Phe-H, yield 88%. 1H-NMR (CDCl3) δ 1.4 (s, 9H, Boc), 3.1 (d, 2H, CH2-Phe), 4.4 (m, 1H, α-H), 5.0 (b, 1H, NH), 7.1-7.3 (m, 5H, Ph), 9.6 (s, 1H, CHO). MS (FAB+) m/z 250 (M+1, 15%), 150 (M−Boc+1, 100%).

Workup

  1. customFehrentz et al., Synthesis (1983), 8, 676

Sources & evidence

ORD record
ord-b61ca3fa564a4eeb8cb029179a77a7af
Source dataset
uspto-grants-2009_04
Patent number
US07521427B2

Reaction notes

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