1,2-Dichloroethane → (3R)-tert-butyl 3-(methoxy(methyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1371519Notes

Reaction equation

HRID 1371519 reaction equation
[N:1]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@@H:2]1[C:11]([OH:13])=O.Cl.[CH3:22]OCN.C1C=C[C:29]2[N:34]([OH:35])N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.C1COCC1>[N:1]1([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@@H:2]1[C:11]([N:34]([O:35][CH3:22])[CH3:29])=[O:13]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 688607(3R)-2-[(tert-butoxy)carbonyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 21959107Methoxymethanamine hydrochloride

Product 1

HCID 86597541(3R)-tert-butyl 3-(methoxy(methyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 75.9%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Boc-D-Tic-OH (4.50 g, 16 mmol), methoxymethylamine hydrochloride (1.56 g, 16 mmol), HOBT (2.43 g, 18 mmol), EDC (3.45 g, 18 mmol), DMAP (200 mg, 1.6 mmol), DIPEA (4.2 ml) and THF (150 ml) are combined, and the resulting mixture is stirred for about 18 hours at r.t. The mixture is stripped to dryness, and the resulting residue is taken up in ethyl acetate and then washed with aqueous HCl (1N), aqueous sodium bicarbonate and brine, which is then dried over sodium sulfate. The solvent is removed and the residue is chromatographed on normal phase (ethylacetate/hexanes 1:1) to give about 3.89 g of Boc-D-Tic-NMeOMe (Weinreb amide).

Workup

  1. washwashed with aqueous HCl (1N), aqueous sodium bicarbonate and brine, which
  2. dry with materialis then dried over sodium sulfate
  3. customThe solvent is removed
  4. customthe residue is chromatographed on normal phase (ethylacetate/hexanes 1:1)

Sources & evidence

ORD record
ord-fbb18be264924fb990ddf69c922decdd
Source dataset
uspto-grants-2007_01
Patent number
US07157463B2

Reaction notes

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