Triphenylphosphine → Methyl 2-{4-[(tert-butoxycarbonyl)amino]butoxy}-6-hydroxybenzoate

HRID 1171931

反応式

HRID 1171931 の反応式
[CH3:1][O:2][C:3](=[O:17])[C:4]1[C:9]([OH:10])=[CH:8][CH:7]=[CH:6][C:5]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][NH2:16].OCC1C=CC=C(CO)C=1C([O-])=O.[C:31]([NH:38][CH:39](O)[CH2:40][CH2:41][CH3:42])([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:17])[C:4]1[C:9]([OH:10])=[CH:8][CH:7]=[CH:6][C:5]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][NH2:16].[CH3:1][O:2][C:3](=[O:17])[C:4]1[C:5]([OH:11])=[CH:6][CH:7]=[CH:8][C:9]=1[O:10][CH2:42][CH2:41][CH2:40][CH2:39][NH:38][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32]

参加物

8

反応物 5

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 11832643Methyl 2-(4-aminobutoxy)-6-hydroxybenzoateHCID 17915834N-Boc aminobutanolHCID 866059492,6-Dihydroxymethylbenzoate

生成物 2

HCID 10980693Methyl 2-{4-[(tert-butoxycarbonyl)amino]butoxy}-6-hydroxybenzoateHCID 11832643Methyl 2-(4-aminobutoxy)-6-hydroxybenzoate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

(2RS)-(4-{2-Benzenesulfonylamino-2-[4-(2-methoxycarbonyl-3-hydroxy-phenoxy)butylcarbamoyl]ethyl}-2-bromophenyl)difluoromethylphosphonic acid diethyl ester (Compound 3A) was prepared from the sulfonamide acid obtained in Example 2B following a procedure similar to Example 2C except that 2-(4-amino-butoxy)-6-hydroxybenzoic acid methyl ester was used instead of phenbutylamine. The 2-(4-amino-butoxy)-6-hydroxy-benzoic acid methyl ester was prepared by taking a solution of 2,6-dihydroxymethylbenzoate (1.0 g, 5.95 mmol), 1.5 equivalents N-Boc aminobutanol and 1.5 equivalents of triphenylphosphine (2.34 g, 8.93 mmol) in 40 mL of CH2Cl2 and adding 1.5 equivalents of DIAD (1.80 g, 8.93 mmol). Stirring continued for 1.5 hours at room temperature. Evaporation to dryness followed by column chromatography (30% EtOAc/hexanes) gave 2-(4-tert-butoxycarbonylamino-butoxy)-6-hydroxy-benzoic acid methyl ester. This compound was cooled to 0° C. in an ice/brine bath. HCl gas was bubbled into the solution for 2 minutes and stirring was continued for 1 hour. Evaporation to dryness followed by precipitation with ether and filtration gave 2-(4-aminobutoxy)-6-hydroxybenzoic acid methyl ester as the HCl salt. Compound 3 was prepared from Compound 3A following the procedures in Example 2D. MS (ion spray):m/z 733.4/735.4 (M−H). 1H NMR: (DMSO-d6, 400 MHz) δ 9.91 (br s, 1H), 8.15 (d, 1H, J=9.2 Hz), 7.94 (br s, 1H), 7.55 (d, 2H, J=8.0 Hz), 7.46 (m, 5H), 7.21 (d, 1H, J=8.0 Hz), 7.15 (t, 1H, J=8.0 Hz), 6.47 (m, 2H), 3.95 (m, 1H), 3.85 (m, 2H), 3.72 (s, 3H), 2.85 (m, 3H), 2.65 (m, 1H), 1.49 (m, 2H), 1.35 (m, 2H).

後処理

  1. customEvaporation to dryness

出典と根拠

ORDレコード
ord-343b301be2944b5fbcdfdbc49b31c388
出典データセット
uspto-grants-2010_11
特許番号
US07829737B2

関連ノート

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