Diisopropylethylamine → 2-[1,1'-Biphenyl]-2-yl-1-morpholin-2-yl-1-tetrahydro-2H-pyran 4-ylethanol hydrochloride

HRID 30329

反応式

HRID 30329 の反応式
[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([CH:16]1[O:21][CH2:20][CH2:19][N:18](CC2C=CC=CC=2)[CH2:17]1)([CH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)[OH:9].CCN(C(C)C)C(C)C.[Cl:44]C(OC(Cl)C)=O>C(Cl)Cl.CO>[ClH:44].[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]([CH:16]1[O:21][CH2:20][CH2:19][NH:18][CH2:17]1)([CH:10]1[CH2:11][CH2:12][O:13][CH2:14][CH2:15]1)[OH:9]

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 588549072-[1,1'Biphenyl]-2-yl-1-[4-(phenylmethyl)morpholin-2-yl]-1-tetrahydro-2H-pyran-4-ylethanol

生成物 1

HCID 684351162-[1,1'-Biphenyl]-2-yl-1-morpholin-2-yl-1-tetrahydro-2H-pyran 4-ylethanol hydrochloride

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

The free base of 56 is obtained from 55 (0.588 g, 1.28 mmol), solid supported Hünig's base (0.72 g) and α-chloroethyl chloroformate (0.53 mL) in anhydrous DCM (20 mL) following General Procedure 3. Purification by ion exchange chromatography gives the free base of 56 as viscous oil (0.483 g), contaminated with a small amount of the N-protected compound 55. The residue is treated with an excess of reagents (1 eq), solid supported Hünig's base (0.36 g) and α-chloroethyl chloroformate (0.26 mL) in anhydrous DCM (20 mL) and methanol (20 mL) and purified by ion exchange chromatography to give the free base of 56 (0.432 g). Purification by preparative LCMS followed by conversion to its hydrochloride salt following General Procedure 4 gives 56 (0.280 g, 54%). MW 403.95; C23H29NO3.HCl; 1H NMR (CD3OD): δ 7.45-7.59 (1H, m), 7.10-7.35 (8H, m), 3.85 (1H, dd, 13 Hz, 3.5 Hz), 3.75 (1H, dd, 11.5 Hz, 3.5 Hz), 3.51-3.59 (3H, m), 2.83-3.12 (7H, m), 2.64 (1H, t, 12 Hz), 1.36-1.52 (2H, m), 1.02-1.21 (2H, m), 0.90-0.94 (1H, m); LCMS: (12 min method) m/z 368 [M−HCl+H]+, RT 4.6 min.

後処理

  1. customPurification by ion exchange chromatography
  2. customgives the free base of 56 as viscous oil (0.483 g)
  3. custompurified by ion exchange chromatography

出典と根拠

ORDレコード
ord-fcc386fbce5f4465b0a62102e3a49dd4
出典データセット
uspto-grants-2008_09
特許番号
US07423037B2

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