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

HRID 30329

반응식

HRID 30329 반응식
[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]

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-fcc386fbce5f4465b0a62102e3a49dd4
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423037B2

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