Ethyl 4-bromobutyrate → (9S)-4-[9-Hydroxycinchonan-6'-yl)oxybutanoic acid

HRID 1599370Notes

Reaction equation

HRID 1599370 reaction equation
C(OC(=O)C([O:8][C:9]1[CH:30]=[C:29]2[C:12]([N:13]=[CH:14][CH:15]=[C:16]2[CH:17]([OH:28])[C@@H:18]2[N:23]3[CH2:24][CH2:25][C@H:20]([C@@H:21]([CH:26]=[CH2:27])[CH2:22]3)[CH2:19]2)=[CH:11][CH:10]=1)CC)C.Br[CH2:33][CH2:34][CH2:35][C:36]([O:38]CC)=[O:37]>>[OH:28][C@@H:17]([C:16]1[C:29]2[C:12](=[CH:11][CH:10]=[C:9]([O:8][CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37])[CH:30]=2)[N:13]=[CH:14][CH:15]=1)[C@@H:18]1[N:23]2[CH2:24][CH2:25][C@H:20]([C@@H:21]([CH:26]=[CH2:27])[CH2:22]2)[CH2:19]1

Participants

3

Reactant 2

HCID 76300Ethyl 4-bromobutyrate2×HCID 131720615HCID 131720615, compound2×

Product 1

HCID 131720614(9S)-4-[9-Hydroxycinchonan-6'-yl)oxybutanoic acid

Procedure

The first step in the synthesis of the tracer of the present invention, as for the hapten, is the alkylation of 6-hydroxyquinidine using preferably one or less molar equivalent of alkylating reagent. The first step is the alkylation of 6-hydroxyquinidine(1) to (9S)-4-[(9-Hydroxycinchonan-6'-yl) oxybutanoic acid ethyl ester (5) using one molar equivalent of ethyl 4-bromobutyrate, most preferably using 0.9 molar equivalent of ethyl 4-bromobutyrate. The alkylated product (5) is hydrolyzed to obtain the corresponding acid (9S)-4-[9-Hydroxycinchonan-6'-yl)oxybutanoic acid (6). The acid is activated to form N-hydroxysuccinimide using a method well-known in the literature. This activated ester is coupled with 5-aminomethylfluorescein in the presence of pyridine to give the quinidine tracer (9S)-N-[(3',6'-dihydroxy-3-oxospiro[isobenzofuran-1(3H),9'-[9H]xanthen]-5yl) methyl]-4-[(9-hydroxycinchonan-6'-yl)oxy]butamide (7).

Workup

  1. customThe first step in the synthesis of the tracer of the present invention

Sources & evidence

ORD record
ord-d62cc742e1954171a7883997abf48b5d
Source dataset
uspto-grants-1998_04
Patent number
US05741715

Reaction notes

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