CN1751021A - 莫达非尼旋光对映异构体的晶形及其制备方法 - Google Patents
莫达非尼旋光对映异构体的晶形及其制备方法 Download PDFInfo
- Publication number
- CN1751021A CN1751021A CNA2003801098134A CN200380109813A CN1751021A CN 1751021 A CN1751021 A CN 1751021A CN A2003801098134 A CNA2003801098134 A CN A2003801098134A CN 200380109813 A CN200380109813 A CN 200380109813A CN 1751021 A CN1751021 A CN 1751021A
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- Prior art keywords
- modafinil
- enantiomer
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- C07B2200/13—Crystalline forms, e.g. polymorphs
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Abstract
Description
CRL 40982形状I | ||
2θ(度) | d() | l/lo(%) |
9.8 | 13.40 | 32 |
15.4 | 8.54 | 87 |
20.8 | 6.34 | 24 |
26.4 | 5.01 | 14 |
28.3 | 4.68 | 19 |
28.7 | 4.62 | 16 |
29.9 | 4.44 | 45 |
31.1 | 4.27 | 100 |
31.6 | 4.20 | 23 |
32 | 4.15 | 14 |
33.1 | 4.02 | 78 |
33.4 | 3.98 | 84 |
34.1 | 3.90 | 16 |
35.1 | 3.80 | 15 |
39 | 3.43 | 22 |
CRL 40982形状II | ||
2θ(度) | d() | l/lo(%) |
11.6 | 11.33 | 54 |
15.4 | 8.54 | 58 |
17.4 | 7.57 | 41 |
17.7 | 7.44 | 34 |
23.3 | 5.67 | 19 |
24.8 | 5.33 | 26 |
27.4 | 4.83 | 19 |
28.9 | 4.59 | 36 |
29.1 | 4.56 | 97 |
29.8 | 4.45 | 23 |
32.8 | 4.05 | 29 |
34.3 | 3.88 | 23 |
35.3 | 3.78 | 100 |
35.9 | 3.71 | 40 |
40.1 | 3.34 | 21 |
47.7 | 2.83 | 20 |
53.7 | 253 | 32 |
CRL 40982形状III | ||
2θ(度) | d() | l/lo(%) |
9.8 | 13.40 | 40 |
10.7 | 12.28 | 39 |
15.4 | 8.54 | 100 |
18.0 | 7.32 | 33 |
21.4 | 6.17 | 23 |
25.9 | 5.11 | 26 |
26.4 | 5.01 | 87 |
29.6 | 4.48 | 26 |
29.9 | 4.44 | 20 |
31.1 | 4.27 | 34 |
31.7 | 4.19 | 20 |
32.4 | 4.10 | 77 |
33.1 | 4.02 | 23 |
33.5 | 3.97 | 64 |
36.5 | 3.66 | 38 |
39.1 | 3.42 | 40 |
41.9 | 3.20 | 32 |
46.4 | 2.91 | 23 |
52.7 | 2.58 | 25 |
CRL 40982形状IV | ||
2θ(度) | d() | l/lo(%) |
6.37 | 13.88 | 26 |
7.14 | 12.38 | 69 |
8.60 | 10.27 | 23 |
10.30 | 8.58 | 100 |
12.04 | 7.34 | 49 |
14.37 | 6.16 | 24 |
15.65 | 5.66 | 11 |
17.30 | 5.12 | 29 |
17.72 | 5.00 | 60 |
19.12 | 4.64 | 15 |
19.81 | 4.48 | 25 |
20.82 | 4.26 | 10 |
21.24 | 4.18 | 12 |
21.70 | 4.09 | 51 |
23.28 | 3.82 | 9 |
24.30 | 3.66 | 30 |
25.18 | 3.53 | 9 |
26.02 | 3.42 | 21 |
27.13 | 3.28 | 9 |
27.90 | 3.20 | 15 |
CRL 40983形状V | ||
2θ(度) | d() | l/lo(%) |
6.65 | 13.27 | 22 |
7.24 | 12.21 | 5 |
9.17 | 9.63 | 51 |
10.38 | 8.51 | 19 |
12.28 | 7.20 | 15 |
14.33 | 6.17 | 14 |
15.81 | 5.60 | 4 |
16.95 | 5.23 | 68 |
17.64 | 5.03 | 100 |
18.69 | 4.74 | 51 |
19.03 | 4.66 | 58 |
20.06 | 4.42 | 3 |
21.06 | 4.22 | 91 |
21.67 | 4.10 | 64 |
22.39 | 3.97 | 17 |
23.61 | 3.77 | 55 |
24.64 | 3.61 | 8 |
25.40 | 3.50 | 13 |
26.21 | 3.40 | 20 |
26.95 | 3.31 | 18 |
碳酸二甲酯溶剂合物 | ||
2θ(度) | d() | l/lo(%) |
7.17 | 12.31 | 38 |
9.12 | 9.69 | 29 |
9.72 | 9.09 | 16 |
10.35 | 8.54 | 35 |
12.17 | 7.27 | 100 |
14.25 | 6.21 | 16 |
16.26 | 5.45 | 10 |
17.36 | 5.10 | 13 |
17.72 | 5.00 | 21 |
18.35 | 4.83 | 9 |
19.16 | 4.63 | 9 |
19.88 | 4.46 | 14 |
21.04 | 4.22 | 12 |
21.49 | 4.13 | 25 |
21.73 | 4.09 | 24 |
23.49 | 3.78 | 22 |
24.55 | 3.62 | 35 |
25.24 | 3.53 | 8 |
26.05 | 3.42 | 9 |
26.88 | 3.32 | 7 |
27.48 | 3.24 | 13 |
27.81 | 3.21 | 10 |
28.79 | 3.10 | 8 |
乙酸溶剂合物 | ||
2θ(度) | d() | l/lo% |
6.64 | 13.30 | 8.5 |
7.15 | 12.35 | 15 |
9.36 | 9.45 | 100 |
10.43 | 8.48 | 6.5 |
12.38 | 7.15 | 25 |
14.38 | 6.16 | 15 |
16.37 | 5.41 | 8 |
17.29 | 5.13 | 28 |
17.82 | 4.97 | 21 |
18.24 | 4.86 | 16 |
18.96 | 4.68 | 7 |
19.24 | 4.61 | 6 |
20.09 | 4.42 | 20 |
21.40 | 4.15 | 75 |
22.55 | 3.94 | 21 |
23.42 | 3.80 | 7 |
24.25 | 3.67 | 40 |
24.92 | 3.57 | 12 |
25.21 | 3.53 | 9.5 |
26.15 | 3.40 | 11 |
26.78 | 3.33 | 8 |
26.99 | 3.30 | 6 |
28.43 | 3.14 | 13 |
28.79 | 3.10 | 14 |
29.63 | 3.01 | 7 |
30.03 | 2.97 | 4 |
32.33 | 2.77 | 9 |
33.13 | 2.70 | 7 |
34.29 | 2.61 | 3 |
34.86 | 2.57 | 7 |
35.90 | 2.50 | 7 |
乙腈合物 | |||
2θ(度) | d() | l/lo(%) | |
5.46 | 16.17 | 46 | |
6.25 | 14.14 | 95 | |
7.17 | 12.32 | 51 | |
8.28 | 10.66 | 81 | |
9.02 | 9.79 | 68 | |
9.51 | 9.29 | 53 | |
10.34 | 8.54 | 53 | |
10.84 | 8.15 | 63 | |
11.33 | 7.80 | 79 | |
12.47 | 7.09 | 53 | |
14.02 | 6.31 | 45 | |
15.20 | 5.83 | 35 | |
15.76 | 5.62 | 34 | |
16.37 | 5.41 | 40 | |
17.37 | 5.10 | 51 | |
18.10 | 4.90 | 46 | |
19.05 | 4.66 | 44 | |
19.36 | 4.58 | 37 | |
19.89 | 4.46 | 39 | |
20.48 | 4.33 | 59 | |
21.14 | 4.20 | 55 | |
22.10 | 4.02 | 100 | |
22.65 | 3.92 | 60 | |
23.17 | 3.835 | 42 | |
23.89 | 3.72 | 33 | |
24.72 | 3.60 | 38 | |
24.93 | 3.57 | 37 | |
25.81 | 3.45 | 37 | |
26.73 | 3.33 | 55 |
27.52 | 3.24 | 30 |
27.97 | 3.19 | 30 |
28.89 | 3.09 | 31 |
29.44 | 3.03 | 27 |
温度 | 域边界 | 平衡相的性质 | 平衡相数 |
TD | A-SD-ID-S′D | 稀释溶液 | 1 |
TD | R-SD-ID | 溶液+R的结晶 | 2 |
TD | S-S′D-ID | 溶液+S的结晶 | 2 |
TD | ID-R-S | 溶液+R和S的结晶 | 3 |
TF | A-SF-IF-S′F | 稀释溶液 | 1 |
TF | R-SF-IF | 溶液+R的结晶 | 2 |
TF | S-S′F-IF | 溶液+S的结晶 | 2 |
TF | IF-R-S | 溶液+R和S的结晶 | 3 |
溶剂 | 1-莫达非尼的量 | 溶剂体积(ml) | 产率 |
甲醇 | 8.37 | ≤50 | 63 |
无水乙醇 | 7.85 | 115 | 56 |
无水乙醇+3%水 | 5 | 70 | 54 |
用甲苯变性的乙醇+3%水 | 5 | 70 | 56 |
水 | 5 | ≥400 | 88 |
溶剂 | 1-莫达非尼的量 | 溶剂体积(ml) | 产率 |
乙酸乙酯 | 6.33 | 385 | 53 |
异丙醇 | 8 | 110 | 69 |
正丙醇 | 7.85 | 65 | 70 |
用甲苯变性的乙醇(2.5%) | 5 | 80 | 54 |
温度(℃) | 10.0 | 20.0 | 30.0 |
质量(%)溶解度 | 3.0 | 4.1 | 5.96 |
过量对映异构体 | 0 | 3.94 | 7.66 | 11.1 |
THOMO(℃) | TL=30 | 32.4 | 34.5 | 36.3 |
温度(℃) | 33.5 | 17 | 17 |
t(分) | 0 | 60 | T滤过 |
温度(℃) | 31.5 | 17 | 17 |
t(分) | 0 | 60 | T滤过 |
溶剂质量 | 质量(±)(g) | 质量(+)(g) | 冷却函数 |
38.38 | 2.43 | 0.3 | I型 |
No. | 纯对映体的质量(g) | 光学纯度(%) |
1 | 0.61 | (+)90.7 |
2 | 0.65 | (-)89.4 |
3 | 0.68 | (+)90.5 |
4 | 0.64 | (-)90.6 |
5 | 0.65 | (+)88.8 |
6 | 0.72 | (-)91.5 |
7 | 0.71 | (+)92.8 |
溶剂质量 | 质量(±)(g) | 质量(+)(g) | 冷却函数 |
511 | 32.42 | 3.99 | I型 |
No. | 纯对映体的质量(g) | 光学纯度(%) |
1 | 8.41 | (+)89.4 |
2 | 8.69 | (-)90.7 |
3 | 8.57 | (+)89.8 |
溶剂质量 | 质量(±)(g) | 质量(+)(g) | 冷却函数 |
1874 | 118.4 | 14.84 | I型 |
No. | 纯对映体的质量(g) | 光学纯度(%) |
1 | 32.1 | (+)89.1 |
2 | 32.3 | (-)90.3 |
3 | 32.5 | (+)91.2 |
4 | 32.9 | (-)89.7 |
5 | 33.1 | (+)90.3 |
6 | 32.7 | (-)90.7 |
7 | 32.9 | (+)90.6 |
溶剂质量 | 质量(±)(g) | 质量(+)(g) | 冷却函数 |
6481 | 408 | 51.32 | I型或II型 |
No. | 纯对映体的质量(g) | 光学纯度(%) | 循环长度 | 冷却函数 |
1 | (+)121.9 | 90.5 | 103 | I |
2 | (-)121.1 | 92.2 | 104 | I |
3 | (+)137.6 | 91.3 | 83 | II |
4 | (-)134.7 | 90.8 | 84 | II |
5 | (+)135.1 | 90.6 | 83 | II |
6 | (-)134.5 | 91.2 | 82 | II |
温度(℃) | 10.0 | 20.0 | 30.0 | 40.0 |
质量(%)溶解度 | 7.4 | 8 | 13.5 | 16 |
过量对映异构体 | 0 | 4% | 6% | 8% |
THOMO(℃) | TL=39 | 44 | 46 | 48 |
溶剂质量 | 质量(±)(g) | 质量(+)(g) |
8000g | 1523 | 132 |
No. | 纯对映体的质量(g) | 光学纯度(%) |
1 | 269.86 | (+)100 |
2 | 300 | (-)97 |
3 | 348.68 | (+)100 |
4 | 369.2 | (-)99.97 |
5 | 413.97 | (+)100 |
6 | 453.2 | (-)95.5 |
7 | 423.8 | (+)98 |
8 | 456 | (-)99.7 |
9 | 494.6 | (+)99.3 |
10 | 485.4 | (-)100 |
11 | 517 | (+)92 |
12 | 487.97 | (-)95.9 |
13 | 471.24 | (+)99.5 |
温度(℃) | 10.0 | 20.0 | 30.0 | 40.0 |
溶解度质量(%) | 7.4 | 9.7 | 13.9 | 25.7 |
对映异构体过量 | 0 | 4% | 6% | 8% | 10% |
THOMO(℃) | TL=45 | 50 | 52 | 53 | 54 |
溶剂质量 | 质量(±)(g) | 质量(+)(g) |
1450g | 501.5 | 55.7 |
No. | 纯对映体的质量(g) | 光学纯度(%) |
1 | 107.1 | (+)99.7 |
2 | 90.9 | (-)78.2 |
3 | 137.1 | (+)72.7 |
4 | 125.5 | (-)84.1 |
5 | 95.9 | (+)94.0 |
6 | 91.6 | (-)88.6 |
7 | 87.0 | (+)85.7 |
8 | 92.2 | (-)88.1 |
9 | 107.0 | (+)104.2 |
10 | 130.6 | (-)120.7 |
11 | 159.9 | (+)111.0 |
12 | 123.3 | (-)113.8 |
13 | 133.0 | (+)130.3 |
14 | 143.0 | (-)134.7 |
15 | 139.2 | (+)128.5 |
16 | 159.4 | (-)127.5 |
17 | 114.0 | (+)111.5 |
18 | 123.4 | (-)120.9 |
19 | 180.6 | (+)99.3 |
20 | 114.2 | (-)110.9 |
21 | 123.1 | (+)120.6 |
22 | 118.4 | (-)115.0 |
23 | 140.1 | (+)135.9 |
24 | 186.2 | (-)118.6 |
25 | 157.1 | (+)106.8 |
26 | 121.2 | (-)102.2 |
27 | 126.5 | (+)122.5 |
28 | 106.6 | (-)99.0 |
溶剂质量 | 质量(±)(g) | 质量(+)(g) | 冷却函数 |
1874 | 118.4 | 14.84 | 从40℃至17℃20分钟=接种温度 |
No. | 纯对映体的质量(g) | 光学纯度(%) |
1 | 30.9 | (+)90.4 |
2 | 31.5 | (-)90.7 |
3 | 31.3 | (+)91.4 |
4 | 31.2 | (-)90.9 |
5 | 31.6 | (+)91.5 |
溶剂质量 | 质量(±)(g) | 质量(+)(g) | 冷却函数 |
1874 | 118.4 | 14.84 | 20分钟从40℃到17℃ |
No. | 质量 | 纯化前的光学纯度(%) |
1 | 25.2 | (+)84.5 |
2 | 24.9 | (-)85.6 |
3 | 25.6 | (+)84.6 |
4 | 25.2 | (-)85.3 |
5 | 24.9 | (+)85.8 |
Claims (63)
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CN2007100017638A Division CN101012189B (zh) | 2002-12-20 | 2003-12-18 | 莫达非尼旋光对映异构体的晶形及其制备方法 |
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